ANNA KARAFOVÁ SYNTEZA PEPTYDÓW ORAZ BADANIE ICH ......– PIŚMIENNICTWO – 6 1. Cox F.E.G....

ANNA KARAFOVÁ

SYNTEZA PEPTYDÓW ORAZ BADANIE ICH

WŁAŚCIWOŚCI

PRZECIWPASOŻYTNICZYCH

Praca wykonana

w Katedrze i Zakładzie Chemii Nieorganicznej

Gdańskiego Uniwersytetu Medycznego

i przedstawiona

Radzie Wydziału Farmaceutycznego

w celu uzyskania stopnia

doktora nauk farmaceutycznych

Promotor rozprawy

dr hab. n. farm. Wojciech Kamysz, prof. nadzw.

Gdańsk 2014

– STRESZCZENIE –

2

Choroby pasożytnicze wywoływane przez pierwotniaki stanowią poważne

obciążenie dla opieki zdrowotnej. Endemiczne głównie w tropikalnych regionach

świata o najniższym statusie ekonomiczno-społecznym, zajmują wiodące miejsce wśród

dziesięciu głównych przyczyn utraty zdrowia i wczesnych zgonów. Brak skuteczności

dostępnych chemioterapeutyków wobec zróżnicowanych stadiów rozwojowych

pasożytów oraz ich zmienność antygenowa, prowadząca do rozwoju lekooporności,

skłaniają do poszukiwania alternatywnych rozwiązań. Szczególną uwagę wielu

środowisk naukowych skupiają peptydy przeciwdrobnoustrojowe (AMPs), będące

głównym elementem wrodzonego układu odpornościowego organizmów

wielokomórkowych. Elementy strukturalne warunkujące ich przeciwbakteryjną

i przeciwgrzybiczą aktywność zostały dobrze poznane, niewiele jednak wiadomo na

temat ich zdolności przeciwpasożytniczych.

Celem pracy było zaprojektowanie i otrzymanie nowych syntetycznych

peptydów w oparciu w właściwości AMPs o potencjalnej aktywności wobec postaci

inwazyjnych pierwotniaków wywołujących choroby tj.: leiszmanioza, trypanosomoza

czy malaria. Określono także ich potencjał cytotoksyczny wobec ludzkich fibroblastów

(MRC-5SV2) i zdolności hemolityczne wobec ludzkich erytrocytów. Ponadto, podjęto

próbę analizy wpływu wprowadzonych modyfikacji strukturalnych na aktywność

przeciwpasożytniczą i przeciwbakteryjną tej grupy związków.

Zaprojektowane peptydy otrzymano metodą syntezy na nośniku stałym

wg strategii Fmoc/tBu, a następnie zanalizowano i oczyszczono przy użyciu

wysokosprawnej chromatografii cieczowej w odwróconym układzie faz (RP-HPLC).

Tożsamość związków potwierdzono dzięki spektrometrii mas MALDI-TOF.

Testy określające właściwości przeciwpasożytnicze i przeciwbakteryjne, a także

charakter cytotoksyczny peptydów zostały wykonane metodą seryjnych rozcieńczeń

w pożywce płynnej w zakresie stężeń 0,25-64 M. Rezultaty przedstawiono

w postaci wartości IC50 wyrażonej jako średnia arytmetyczna z wyników uzyskanych

z dwóch niezależnych eksperymentów odchylenie standardowe (SD). Sprecyzowano

również wartości minimalnego stężenia, przy którym peptydy wykazywały zdolność do

hemolizy ludzkich erytrocytów (MHC). Ponadto, wyznaczono wartości indeksu

selektywności (SI) jako stosunek IC50 aktywności cytotoksyczej peptydów do

– STRESZCZENIE –

3

IC50 aktywności przeciwpasożytniczej lub przeciwbakteryjnej, który jest kluczowym

parametrem na etapie identyfikacji nowych związków, jako potencjalnych leków

przeciwpasożytniczych.

Na podstawie uzyskanych danych zaobserwowano, że żaden z otrzymanych

peptydów nie wykazywał charakteru cytotoksycznego i hemolitycznego w zakresie

działania terapeutycznego. Potwierdzono, że wzrost ładunku peptydu spowodowany

obecnością zasadowych reszt aminokwasowych i redukcja heliakalnego oraz

hydrofobowego charakteru związku prowadziły do spadku jego aktywności

hemolitycznej i zwiększenia stopnia selektywności wobec zdrowych komórek. Ponadto,

część związków odznaczała się wysokim potencjałem przeciwpasożytniczym,

a wartości IC50 określające ich aktywność wobec S. aureus i E. coli była znacznie

niższe niż dla konwencjonalnych antybiotyków tj.: erytromycyna czy chloramfenikol.

Stwierdzono, że przyłączenie układu steroidowego (reszty kwasu

deoksycholowego, DOCA) do peptydu pozbawionego natywnych wiązań disulfidowych

pozwala na zachowanie jedynie aktywności przeciwbakteryjnej.

Wprowadzenie pojedynczego wiązania disulfidowego do struktury związku,

a także zamiana reszty fenyloalaniny na resztę kwasu p-aminobenzoesowego (PABA)

może stanowić skuteczną metodę, prowadzącą do wzrostu selektywnego charakteru

związku.

Wysoki potencjał przeciwpasożytniczy i przeciwbakteryjny, a także brak

cytotoksycznych i hemolitycznych właściwości wybranych analogów może przesądzić

o potencjalnym ich wykorzystaniu w terapii kombinowanej z powszechnie stosowanymi

chemioterapeutykami. Scharakteryzowanie wpływu wprowadzonych modyfikacji

strukturalnych na aktywność biologiczną otrzymanych peptydów może znacznie

ułatwić dalsze poszukiwanie aktywnych związków.

– SUMMARY –

4

Parasitic diseases caused by Protozoa are a serious burden for health care.

Endemic mainly in tropical regions of the world with the lowest socio-economic status,

occupy the leading place among ten major causes of health problems and premature

death. Lack of efficacy of available chemotherapeutic agents to different developmental

stages of the parasites and their antigenic variation, leading to drug resistance, induce

the need to search for alternative solutions. Antimicrobial peptides (AMPs), constituting

the main component of the innate immune system of multicellular organisms, attract

attention of many research groups. Structural features ensuring their antibacterial and

antifungal activity are well known, but little is known about their antiparasitic

properties.

The aim of this study was to develop and prepare novel synthetic peptides based

on AMPs properties with potential activity against invasive forms of protozoa causing

the diseases such as leishmaniasis, trypanosomiasis and malaria. Their cytotoxic

potential against human fibroblasts (MRC-5SV2) and haemolytic activity against human

erythrocytes was determined. Additionally, an attempt has been made to analyze the

impact of structural modifications on the antiparasitic and antibacterial activity of this

group of compounds.

The designed peptides were obtained by solid phase peptide synthesis (SPPS)

using Fmoc/tBu strategy, and then analyzed and purified by reversed-phase high-

performance liquid chromatography (RP-HPLC). Identity of the compounds was

confirmed by MALDI-TOF mass spectrometry.

Tests for the antiparasitic and antibacterial activities, and cytotoxic character of

the peptides have been carried out by serial dilution method in a liquid medium over the

concentration range of 0,25-64 M. The results are presented as IC50 values expressed

as the arithmetic mean of two independent experiments standard deviation (SD). The

minimum concentration at which the peptides were able to hemolyze the human

erythrocytes (MHC) was also determined. Furthermore, the values of the selectivity

index (SI) were calculated as the ratio of IC50 of cytotoxic activity of the peptides to the

IC50 of antiparasitic or antibacterial activity, which is a crucial parameter for identifying

the new compounds as potential antiparasitic drugs.

– SUMMARY –

5

The data showed that none of the peptides had cytotoxic and haemolytic

character over the range of their therapeutic concentrations. It was confirmed that the

increase in charge of the peptide due to the presence of basic amino acid residues and

reduction of its hydrophobic and helical nature decreased its haemolytic activity and

increased the degree of selectivity towards health human cells. Moreover, some

compounds possessed high antiparasitic potential, while IC50 values indicating their

activity against S. aureus and E. coli were much lower than for conventional antibiotics

such as erythromycin or chloramphenicol.

It has been found that the attachment of the steroid skeleton (deoxycholic acid

residue, DOCA) to a peptide devoid of native disulphide bonds preserves only

the antimicrobial activity.

The introduction of a single disulfide bond to a peptide structure, and

the substitution of phenylalanine residue with p-aminobenzoic acid (PABA) may be

an effective method, leading to an increase in compound selectivity.

High antiparasitic and antibacterial potential of some peptides, as well as

the lack of cytotoxic and haemolytic effect on human cells allow to suggest their

potential use in combination therapy with commonly used chemotherapeutic agents.

Characterization of the effect of structural modifications on the biological activity

of the peptides can greatly facilitate further search for new active compounds.

– PIŚMIENNICTWO –

6

1. Cox F.E.G. History of human parasitology. Clin. Microbiol. Rev. 15, 2002, 595-612.

2. Deryło A. Parazytologia i akaroentomologia medyczna. Warszawa, Wydawnictwo

Naukowe PWN, 2011

3. Zhang Y., MacArthur C., Mubila L., Baker S. Control of neglected tropical diseases

needs a long-term commitment. BMC Med. 8, 2010, art. No doi: 10.1186/1741-7015-8-

67.

4. Hotez P.J., Savioli L., Fenwick A. Neglected tropical diseases of the Middle East and

North Africa: review of their prevalence, distribution and opportunities for control. PLoS

Negl. Trop. Dis.6, 2012, art. No doi: 10.1371/journal.pntd.0001475.

5. Zofou D., Nyasa R.B., Nsagha D.S., Ntie-Kang F., Meriki H.D., Assob J.C.N., Kuete V.

Control of malaria and other vector-borne protozoa diseases in the tropics: enduring

challenges despite considerable progres and achievements. Infect. Dis. Poverty 3, 2014,

art. No doi: 10.1186/2049-9957-3-1.

6. Magdzik W., Naruszewicz-Lesiuk D., Zieliński A. Choroby zakaźne i pasożytnicze –

epidemiologia i profilaktyka. Bielsko-Biała, -medica Press, 2004.

7. Astelbauer F., Walochnik J. Antiprotozoal compounds: state of the art. And new

developments. Int. J. Antimicrob. Agents. 38, 2011, 118-124.

8. Murphy S.C., Shott J. P., Parikh S., Etter P., Prescott W.R., Stewart V.A. Review article:

Malaria Diagnostics in clinical trials. Am. J. Trop. Hyg. 89, 2013, 824-839.

9. Askling H.H., Bruneel F., Burchard G., Castelli F., Chiodini P.L., Grobusch M.P., Lopez-

Velez R., Paul M., Petersen E., Popescu C., Ramharter M., Schlagenhauf P. Management

of imported malaria in Europe. Malar. J. 11, 2012, art. No doi: 10.1186/1475-2875-11-

328.

10. Stępień M. Malaria in Poland in 2011. Przegl. Epidemiol. 67, 2013, 373-374.

11. Barret M.P., Croft S.L. Management of trypanosomiasis and leishmaniasis. Br. Med. Bull.

104, 2012, 175-196.

12. Nakayima J., Nakao R., Alhassan A., Mahama G., Afakye K., Sugimoto C. Molecular

epidemiological studies on animal trypanosomiases in Ghana. Parasit. Vectors. 5, 2012,

art. No doi: 10.1186/1756-3305-5-217.

13. Pawłowski Z.S., Stefaniak J. Parazytologia kliniczna w ujęciu wielodyscyplinarnym.

Warszawa, Wydawnictwo Lekarskie PZWL, 2004.

14. World Health Organization. Control and surveillance of human African trypanosomiasis.

WHO Tech. Rep. Ser. 984, 2013, 1-237.

15. McGwire B.S., Olson C.L., Tack B.F., Engman D.M. Killing of African Trypanosomes

by antimicrobial peptides. JID 188, 2003, 146-152.


7

16. Balana-Fouce R., Reguera R.M., Cubria J.C., Ordonez D. The pharmacology of

Leishmaniasis. Gen. Pharmac. 30, 1998, 435-443.

17. Tiuman T.S., Santos A.O., Ueda-Nakamura T., Dias Filho B.P., Nakamura C.V. Recent

advances in leishmaniasis treatment. Int. J. Infect. Dis. 15, 2011, 525-532.

18. Gerald N., Mahajan B., Kumar S. Mitosis in the human malaria parasites Plasmodium

falciparum. Eucaryot. Cell. 10, 2011, 474-482.

19. Collier L., Balows A., Sussman M. Topley&Wilson’s Microbiology and microbial

infections. London, Arnold 1999.

20. Ayisi N.K., Appiah-Opong R., Gyan B., Bugyei K., Ekuban F. Plasmodium falciparum:

Assessment of selectivity of action of chloroquine, Alchornea cordifolia, Ficus polita,

and other drugs by a tetrazolium–based colorimetric assay. Malar. Res. Treat. 2011,

2011, art. No doi: 10.4061/2011/816250.

21. McMorran B.J., Marshall V.M., de Graff C., Drysdale K.E., Shabbar M., Smyth G.K.,

Corbin J.E., Alexander W.S., Foote S.J. Platelets kill intraerythrocytic malarial parasites

and mediate survival to infection. Science 6, 2009, 797-800.

22. Mackintosh C.L., Beeson J.G., Marsh K. Clinical features and pathogenesis of severe

malaria. Trends. Parasitol. 20, 2004, 597-603.

23. Autino B., Corbett Y., Castelli F., Taramelli D. Pathogensis of malaria in tissues and

blood. Mediterr. J. Hematol. Infect. Dis. 4, 2012, art. No doi: 10.4084/MJHID.2012.061.

24. de Souza W., de Carvalho T.M., Barrias E.S. Review on Trypanosoma cruzi: Host cel

interaction. Int. J. Cell Biol. 2010, 2010, art. No doi: 10.1155/2010/295394.

25. Barrias E.S., de Carvalho T.M., de Souza W. Trypanosoma cruzi: entry into mammalian

host cells and parasitophorous vacuole formation. Front. Immunol. 4, 2013, art. No doi:

10.3389/fimmu.2013.00186.

26. World Health Organization. Control of Chagas disease.WHO Tech. Rep. Ser. 905,

Geneva 2002, 1-109.

27. Kennedy P.G.E. Clinical features, diagnosis and treatment of human African

trypanosomiasis (sleeping sickness). Lancet. Neurol. 12, 2013, 186-194.

28. Stockdale C., Swiderski M.R., Barry D.J., McCulloch R. Antigenic variation in

Trypanosoma brucei: joining the DOTs. PLoS Biol. 6, 2008, art. No. doi:

10.1371/journal.pbio.0060185.

29. Stich A., Abel P.M., Krishna S. Human African trypanosomiasis. BMJ 325, 2002,

203-206.

30. Kennedy P.G.E. Difficulties in diagnostic staging of human African trypanosomiasis.

J. Neuroparasitol. 2, 2011, 1-3.


8

31. Sundar S., Rai M. Laboratory diagnosis of visceral leishmaniasis. Clin. Diagn. Lab.

Immunol. 9, 2002, 951-958.

32. Assche T.V., Deschacht M., Inocencio da Luz R.A., Maes L., Cos P. Leishmania -

macrophage interactions: Insights into the redox biology. Free Radic. Biol. Med. 51,

2011, 337-351.

33. Mohebali M. Visceral leishmaniasis in Iran: Review of the epidemiological and clinical

features. Iran. J Parasitol. 8, 2013, 348-358.

34. Chappuis F., Sundar S., Hailu A., Ghalib H., Rijal S., Peeling R.W., Alvar J., Boelaert M.

Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?. Nat. Rev.

Microbiol. 5, 2007, 873-882.

35. Stich A., Ponte-Sucre A., Holzgrabe U. Do we need new drugs against African

trypanosomiasis? Lancet. Infect. Dis. 13, 2013, 733-734.

36. Keiser J., Stich A., Burri C. New drugs for the treatment of human African

trypanosomiasis: research and development. Trends. Parasitol. 17, 2001, 42-49.

37. Otoguro K., Iwatsuki M., Ishiyama A., Namatame M., Nishihara-Tukashima A.,

Shibahara S., Kondo S., Yamada H., Omura S. Promising lead compounds for novel

antiprotozoals. J. Antibiot. (Tokyo) 63, 2010, 381-384.

38. Shaji J., Jain V. Solid lipid nanoparticles: a novel carrier for chemotherapy. Int. J.

Pharmacy and Pharm. Sci. 2, 2010, 8-17.

39. Jain K., Sood S., Gowthmarajan K. Lipid nanocarriers and molecular targets for malaria

chemotherapy. Curr. Drug Targets 15, 2014, 292-312.

40. Davis A.J., Kedzierski L. Recent advances in antileishmanial drug development. Curr.

Opin. Investig. Drugs 6, 2005, 163-169.

41. Barret M.P., Mottram J.C., Coombs G.H. Recent advances in indentifying and validating

drug targets in trypanosomes and leishmanias. Trends Microbiol. 7, 1999, 82-88.

42. Fairlamb A.H., Ridley R.G., Vial H.J. Drugs against parasitic diseases: R&D

methodologies and issues. Discoveries and drug development. WHO 2003,1-220.

43. Peng Y., Keenan S.M., Welsh W.J. Structural model of Plasmodium CDK, Pfmrk,

a novel target for malaria therapeutics. J. Mol. Graph. Model. 24, 2005, 72-80.

44. Mackiewicz P., Gagat P., Bodył A. Genomika protistów – bardzo zróżnicowanych, ale

słabo poznanych eukariotów. Biotechnologia 4, 2010, 91-130.

45. Padmanaban G. Drug targets in malaria parasites. Adv. Biochem. Engin/Biotechnol. 84,

2003, 123-141.


9

46. Padmanaban G., Nagaraj V.A., Rangarajan P.N. Drugs and drug targets against malaria.

Curr. Sci. 92, 2007, 1545-1555.

47. Aguiar A.C., Rocha E.M., Souza N.B., Franca T.C.C., Krettli A.U. New approaches in

atimalarial drug discovery and development: a review. Mem. Inst. Oswaldo Cruz 107,

2012, 831-845.

48. Maya J.D., Cassels B.K., Iturriaga-Vasquez P., Ferreira J., Faundez M., Galanti N.,

Ferreira A., Morello A. Mode of action of natural and synthetic drugs against

Trypanosoma cruzi and their interaction with the mammalian host. Comp. Biochem.

Physiol. A Mol. Integr. Physiol. 146, 2007, 601-620.

49. Regules J.A., Cummings J.F., Ockenhouse C.F. The RTS,S vaccine candidate for

malaria. Expert Rev. Vaccines 10, 2011, 589-599.

50. Biamonte M.A., Wanner J., Le Roch K.G. Recent advances in malaria drug discovery.

Bioorg. Med. Chem. Lett. 23, 2013, 2829-2843.

51. Rodgers J., Jones A., Gibaud S., Bradley B., McCabe C., Barret M.P., Gettinby G.,

Kennedy P.G.E. Melarsoprol cyclodextrin inclusion complexes as promising oral

candidates for the treatment of human African trypanosomiasis. PLoS Negl. Trop. Dis. 5,

2011, art. No doi: 10.1371/journal.pntd.0001308.

52. Machado F.S., Tanowitz H.B., Teixeira M.M. New drugs for neglected infectious

diseases: Chagas’disease. Br. J. Pharmacol. 160, 2010, 258-259.

53. Castro J.A., de Mecca M.M., Bartel L.C. Toxic side effects of drugs used to treat Chagas’

disease (American trypanosomiasis). Hum. Exp. Toxicol. 25, 2006, 471-479.

54. Roberts W.L., Mcmurray W.J., Rainey P.M. Characterization of the antimonial

antileishmanial agent meglumine antimonate (Glucantime). Antimicrob. Agents

Chemother. 42, 1998, 1076-1082.

55. Neelagiri S., Kumar S., Singh S. Tools for antileishmanial drug discovery and drug

development. Curr. Res. Infor Pharm Sci. 11, 2010, 22-28.

56. Ouellette M., Drummelsmith J., Papadopoulou B. Leishmaniasis: drugs in the clinic,

resistance and new developments. Drug Resist. Updat. 7, 2004, 257-266.

57. Singh N. Drug resistance mechanisms in clinical isolates of Leishmania donovani. Indian

J. Med. Res. 123, 2006, 411-422.

58. Cobb S.L., Denny P.W. Antimicrobial peptides for leishmaniasis. Curr. Opin. Investig.

Drugs. 11, 2010, 868-875.

59. Doonan S. Białka i peptydy. Warszawa, Wydawnictwo Naukowe PWN, 2008.

60. Jakubke H.D., Jeschkeit H. Aminokwasy, peptydy, białka. Warszawa, Wydawnictwo

Naukowe PWN, 1989.


10

61. Galdiero S., Falanga A., Cantisani M., Vitiello M., Morelli G., Galdiero M. Peptide-lipid

interactions: experiments and applications. Int. J. Mol. Sci. 14, 2013, 18758-18789.

62. Marino S.M., Gladyshev V.N. Analysis and functional prediction of reactive cysteine

residues. J. Biol. Chem. 287, 2012, 4419-4425.

63. Andrès E., Dimarcq J.K. Peptides antimicrobiens cationiques: de l’étude de l’immunité

innée à la production de médicaments.Mise à jour. Med. Mal. Infect. 37, 2007, 194-199.

64. Korting H.C., Schollmann C., Stauss-Grabo M., Schafer-Korting M. Antimicrobial

peptides and skin: a paradigm of translational medicine. Skin Pharmacol. Physiol. 25,

2012, 325-334.

65. Baltzer S.A., Brown M. Antimicrobial peptides – promising alternatives to conventional

antibiotics. J. Mol. Microbiol. Biotechnol. 20, 2012, 228-235.

66. Boman H.G. Antibacterial peptides: basic facts and emerging concept. J. Intern. Med.

254, 2003, 197-215.

67. Mangoni M.L., Shai Y. Short native antimicrobial peptides and engineered ultrashort

lipopeptides: similarities and differences in cel specifities and modes of action. Cell. Mol.

Life. Sci. 68, 2011, 2267-2280.

68. Zasloff M., Martin B., Chen H.C. Antimicrobial activity of synthetic magainin peptides

and several analogues. Proc. Natl. Acad. Sci. USA 85, 1988, 910-913.

69. Pretzel J., Mohring F., Rahlfs S., Becker K. Antiparasitic peptides. Adv. Biochem. Eng.

Biotechnol. 135, 2013, 157-192.

70. Guani-Guerra E., Santos-Mendoza T., Lugo-Reyes S.O., Teran L.M. Antimicrobial

peptides: General overview and clinical implications in human health and disease. Clin.

Immunol. 135, 2010, 1-11.

71. Nizet V., Gallo R.L. Cathelicidins and innate defense against invasive bacterial infection.

Scand. J. Infect. Dis. 35, 2003, 670-676.

72. Silva P.M., Gonçalves S., Santos N.C. Defensins: antifungal lessons from eukaryotes.

Front. Microbiol. 5, 2014, art. No doi: 10.3389/fmicb.2014.00097.

73. Żyłowska M., Wyszyńska A., Jagusztyn-Krynicka E.K. Defensyny – peptydy o

aktywności przeciwbakteryjnej. Post. Mikrobiol. 50, 2011, 223-234.

74. Lazaridis T., He Y., Prieto L. Membrane interactions and pore formation by the

antimicrobial peptide protegrin. Biophys. J. 104, 2013, 633-642.

75. Bolintineanu D.S., Kaznessis Y.N. Computational studies of protegrin antimicrobial

peptides: a review. Peptides 32, 2011, 188-201.


11

76. Otvos L Jr. The short proline-rich antibacterial peptide family. Cell Mol. Life Sci. 59,

2002, 1138-1150.

77. Stalmans S., Wynendaele E., Bracke N., Knappe D., Hoffmann R., Peremans K., Polis I.,

Burvenich C., De Spiegeleer B. Blood-brain barrier transport of short proline-rich

antimicrobial peptides. Protein Pept. Lett. 21, 2014, 399-406.

78. Zhou Y., Peng Y. Synergistic effect of clinically used antibiotics and peptide antibiotics

against gram-positive and gram-negative bacteria. Exp. Ther Med. 6, 2013, 1000-1004.

79. Raaijmakers J.M., Bruijn I., Nybroe O., Ongena M. Natural functions of lipopeptides

from Bacillus and Pseudomonas: more than surfactants and antibiotics. FEMS Microbiol.

Rev. 34, 2010, 1037-1062.

80. Shai Y., Makovitzky A., Avrahami D. Host defense peptides and lipopeptides: modes of

action and potential candidates for the treatment of bacterial and fungal infections. Curr.

Protein Pept. Sci. 7, 2006, 479-486.

81. Pirri G., Guliani A., Nicoletto S.F., Pizzuto L., Rinaldi A.C. Lipopeptides as anti-

infectives: a practical perspectives. Cent. Eur. J. Biol. 4, 2009, 258-273.

82. Mandal S.M., Barbosa A.E.A.D., Franco O.L. Lipopeptides in microbial infection

control: scope and reality for industry. Biotechnol. Adv. 31, 2013, 338-345.

83. Kulkarni M.M., Karafova A., Kamysz W., Schenkman S., Pelle R., McGwire B.S.

Secreted Trypanosome cyclophilin inactivates lytic insect defense peptides and induces

parasites calcineurin activation and infectivity. J. Biol. Chem. 288, 2013, 8772-8784.

84. Torrent M., Pulido D., Rivas L., Andreu D. Atimicrobial peptide action on parasites.

Curr. Drug Targets 13, 2012, 1138-1147.

85. Cirimotich C.M., Dong Y., Clayton A.M., Sandiford S.L., Souza-Neto J.A., Mulenga M.,

Dimopoulos G. Natural microbe-mediated refractoriness to Plasmodium infection in

Anopheles gambiae. Science 332, 2011, 855-858.

86. Boulanger N., Bulet P., Lowenberger C. Antimicrobial peptides in the interactions

between insects and flagellate parasites. Trends Parasitol. 22, 2006, 262-268.

87. Trabulo S., Cardoso A.L., Cardoso A.M., Morais C.M., Jurado A.S., Pedroso de Lima

M.C. Cell-penetrating peptides as nucleic acid delivery systems: from biophysics to

biological applications. Curr. Pharm. Des. 19, 2013, 2895-923.

88. Shai Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer

membranes by -helical antimicrobial and cel non-selective membrane-lytic peptides.

Biochim. Biophys. Acta 1462, 1999, 55-70.

89. Jelinek R., Kolusheva S. Membrane interactions of host-defense peptides studied in

model systems. Curr. Protein Pept. Sci. 6, 2005, 103-114.


12

90. Brandenburg L.O., Merres J., Albrecht L.J., Varoga D., Pufe T. Antimicrobial peptides:

multifunctional drugs for different applications. Polymers 4, 2012, 539-560.

91. Nicolas P. Multifunctional host defense peptides: intracelullar targeting antimicrobial

peptides. FEBS J. 276, 2009, 6483-6496.

92. Bahar A.A., Ren D. Antimicrobial peptides. Pharmaceuticals (Basel.) 6, 2013,

1543-1575.

93. Brogden N.K., Brogden K.A. Will new generations of modified antimicrobial peptides

improve their potential as pharmaceuticals? Int. J. Antimicrob. Agents. 38, 2011, 217-225.

94. Mitchell A.R. Bruce Merrifield and solid-phase peptide synthesis: a historical assessment.

Biopolymers. 90, 2008, 175-184.

95. Pushpanathan M., Gunasekaran P., Rajendhran J. Antimicrobial peptides: versatile

biological properties. Int. J. Pept. 2013, 2013, art. No doi: 10.1155/2013/675391.

96. Silverman R.B. Chemia organiczna w projektowaniu leków. Warszawa, Wydawnictwo

Naukowo-Techniczne, 2004.

97. Witt K.A., Gillespie T.J., Huber J.D., Egleton R.D., Davis T.P. Peptide drug

modifications to enhance bioavailability and blood-brain barrier permeability. Peptides

22, 2001, 2329-2343.

98. Rivera D.G., Vasco A.V., Echemendía R., Concepción O., Pérez C.S., Gavín J.A.,

Wessjohann L.A. A multicomponent conjugation strategy to unique N-steroidal peptides:

first evidence of the steroidal nucleus as a β-turn inducer in acyclic peptides.

Chem. Eur. J. 20, 2014, 13150-13161.

99. Wimley W.C., Hristova K. Antimicrobial peptides: successes, challenges and unanswered

questions. J. Membrane Biol. 239, 2011, 27-34.

100. Ronga L., Verdié P., Sanchez P., Enjabal C., Maurras A., Jullian M., Puget K., Martinez

J., Subra G. Supported oligomethionine sulfoxide and Ellman’s reagent for cysteine

Bridges formation. Amino Acids 44, 2013, 733-742.

101. Harwig S.S.L., Waring A., Yang H.J., Cho Y., Tan L., Lehrer R.I. Intramolecular

disulfide bonds enhance the antimicrobial and lytic activities of protegrins at

physiological sodium chloride concentrations. Eur. J. Biochem. 240, 1996, 352-357.

102. Hwang H., Hyun S., Kim Y., Yu J. Reduction of helical content by insertion of a

disulfide bond to an antimicrobial peptide with decreased hemolytic activity.

Chem.Med.Chem. 8, 2013, 59-62.

103. http://crdd.osdd.net/raghava/parapep/submitkey_browse.php?ran=9863.

104. Atherton E., Sheppard R.C. Solid phase peptide synthesis: A practical approach (The

practical approach series). Oxford, Oxford University Press, 1989.


13

105. Mergler M., Durieux J.P. The Bachem practice of SPPS: Tips and tricks from the experts

at Bachem. Bachem AG, 2005.

106. Fields G.B., Noble R. L. Solid phase peptide synthesis utilizing 9–fluorenyl–

methoxycarbonyl amino acids. Int. J. Pept. Protein. Res. 35, 1990, 161-214.

107. Chan W.C., White P.D. Fmoc solid phase peptide synthesis. A practical approach. New

York, Oxford University Press, 2004.

108. Shelton P.T., Jensen K.J. Linkers, resins, and general procedures for solid–phase peptide

synthesis. Methods for Molecular Biology 1047. Peptide synthesis and applications. New

York, Humana Press, 2013.

109. NovaBiochem. The fine art of solid phase synthesis including synthesis notes and the

polimer supported reagents handbook. NovaBiochem, Germany 2002/3.

110. Christensen T. Qualitative test for monitoring coupling completeness in solid phase

peptide synthesis using chloranil. Acta Chem. Scand. Ser. B 33, 1979, 763-766.

111. Kamysz E., Sikorska E., Karafova A., Dawgul M. Synthesis, biological activity and

conformational analysis of head-to-tail cyclic analogues of LL37 and histatin 5. J. Pept.

Sci. 18, 2012, 560-566.

112. Dick F. Acid cleavage/deprotection in Fmoc/tBu solid-phase peptide synthesis. Methods

in molecular biology 35. Peptide synthesis protocols. New Jersey, Humana Press, 1994.

113. Carpino L.A., Shroff H., Triolo S.A., Mansour E.M.E., Wenschuh H., Albericio F. The

2,2,4,6,7- pentamethyldihydrobenzofuran-5-sulfonyl group (Pbf) as arginine side chain

protectant. Tetrahedron Lett. 34, 1993, 7829-7832.

114. Boulègue C., Musiol H.J., Prasad V., Moroder L. Synthesis of cysteine-rich peptides.

Chem. Today 24, 2006, 24-36.

115. Wang X.Y, Wang Q., Huang X.Y., Wang T., Yu X.Q. Synthesis of small cyclic peptides

containing disulfide bond. Arkivoc 2006, 2006, 148-154.

116. Cos P., Vlietinck A.J., Berghe D.V., Maes L. Anti-infective potential of natural products:

How to develop a stronger in vitro ‘proof-of-concept’. J. Ethnopharmacol. 106, 2006,

290-302.

117. Huschtscha L.I., Holliday R. Limited and unlimited growth of SV40-transformed cells

from human diploid MRC-5 fibroblasts. J. Cell Sci. 63, 1983, 77-99.

118. Sikora E. Nieśmiertelność, starzenie i śmierć komórek. Rola protoonkogenów,

onkogenów i antyonkogenów. Post. Bioch. 39, 1993, 212-220.

119. Mesia K., Cimanga R.K., Dhooghe L., Cos P., Apers S., Totté J., Tona G.L., Pieters L.,

Vlietinck A.J., Maes L. Antimalarial activity and toxicity evaluation of a quantified

Nauclea pobeguinii extract. J. Ethnopharmacol. 131, 2010, 10-16.


14

120. Trager W., Jensen J.B. Human malaria parasites in continous culture. J. Parasitol. 91,

2005, 484-486.

121. Desjardins R.E., Canfield C.J., Haynes J.D., Chulay J.D. Quantitative assessment of

antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob.

Agents Chemother. 16, 1979, 710-718.

122. Mothana R.A., Al.-Musayeib N.M., Al.-Ajmi M.F., Cos P., Maes L. Evaluation of the in

vitro antiplasmodial, antileishmanial, and antitrypanosomal activity of medicinal plants

used in Saudi and Yemeni tradicional medicine. Evid. Based Complement Alternat. Med.

2014, 2014, art. No. doi. 10.1155/2014/905639.

123. Ehata M.T., Phuati A.M., Lumpu S.N., Munduku C.K., Phongi D.B., Lutete G.T.,

Kabangu O.K., Kanyanga R.C., Matheeussen A., Cos P., Apers S., Pieters L., Maes L.,

Vlietinck A.J. In vitro antiprotozoal and cytotoxic activity of the aqueous extract , the

80% methanol extract and its fractions from the seeds of Brucea sumatrana Roxb.

(Simaroubaceae) growing in Democratic Republic of Congo. Chin. Med. 3, 2012, 65-71.

124. El Bissati K., Zufferey R., Witola W.H., Carter N.S., Ullman B., Mamoun C.B. The

plasma membrane permease PfNT1 is essential for purine salvage in the human malaria

parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 103, 2006, 9286-9291.

125. Makler M.T., Ries J.M., Williams J.A., Bancroft J.E., Piper R.C., Gibbins B.L., Hinrichs

A.D. Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug

sensitivity. Am. J. Trop. Med. Hyg. 48, 1993, 739-741.

126. Makler M.T., Henrichs A.D. Measurement of the lactate dehydrogenase activity of

Plasmodium falciparum as an assessment of parasitemia. Am. J. Trop. Med. Hyg. 48,

1993, 205-210.

127. Krzysztoń – Russjan J., Książek I., Anuszewska E. Porównanie użyteczności testów MTT

i EZ4U stosowanych do oceny cytotoksyczności ksenobiotyków. Farm. Pol. 65, 2009,

395-402.

128. TDR, Lead discovery for drugs. Business Plan 2008-2013, BL 3, 2007.

129. Buckner F.S., Verlinde C.L., La Flamme A.C., Van Voorhis W.C., Efficient technique for

screening drugs for activity against Trypanosoma cruzi using parasites expressing beta –

galactosidase. Antimicrob. Agents Chemother. 40, 1996, 2592-2597.

130. Le – Senne A., Muelas – Serrano S., Fernandez – Portillo C., Escario J.A., Gomez –

Barrio A. Biological characterization of a β – Galactosidase expressing clone of

Trypanosoma cruzi CL strain. Mem. Inst. Oswaldo Cruz 97, 2002, 1101-1105.

131. http://lib.store.yahoo.net/lib/yhst-131428861332406/A10100K-CPRG-B-gal-Assay-Kit-

Manual.pdf

132. Berg M., Kohl L., Van der Veken P., Joossens J., Al.-Sabi M.I., Castagna V., Giannese

F., Cos P., Versées W., Steyaert J., Grellier P., Haemers A., Degano M., Maes L., de


15

Koning H.P., Augustyns K. Evaluation of nucleoside hydrolase inhibitors for treatment of

African trypanosomiasis. Antimicrob. Agents Chemother. 54, 2010, 1900-1908.

133. http://www.who.int/tdr/grants/workplans/en/African_tryps_invitro.pdf

134. Ponte-Sucre A., Díaz E., Padrón-Nieves M. Drug resistance in Leishmania parasites.

Consequences, molecular mechanisms and possible treatments. Wiedeń, Springer 2013.

135. Räz B., Iten M., Grether-Bühler Y., Kaminsky R., Brun R. The Alamar Blue® assay to

determine drug sensitivity of African trypanosomes (T. b. rhodesiense and T. b.

gambiense) in vitro. Acta Trop. 68, 1997, 139-147.

136. O’Brien J., Wilson I., Orton T., Pognan F. Investigation of Alamar Blue (resazurin)

fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur. J. Biochem. 267,

2000, 5421-5426.

137. Promega. Technical Bulletin CellTiter-Blue® Cell Viability Assay. Instructions for use of

products G8080, G8081, G8082. USA 2006.

138. Hirumi H., Hirumi K. Continous cultivation of Trypanosoma brucei blood stream forms

in a medium containing a low concentration of serum protein without feeder cel layers. J.

Parasitol. 75, 1989, 985-989.

139. Falcão S.I., Vale N., Cos P., Gomes P., Freire C., Maes L., Vilas-Boas M. In vitro

evaluation of Portuguese Propolis and floral sources for antiprotozoal, antibacterial and

antifungal activity. Phytother. Res. 28, 2014, 437-443.

140. da Luz R.I., Vermeersch M., Dujardin J.C., Cos P., Maes L. In vitro sensitivity testing of

Leishmania clinical field isolates: preconditioning of promastigotes enhances infectivity

for macrophage host cells. Antimicrob. Agents Chemother. 53, 2009, 5197-5203.

141. http://imaging.omrf.org/wp-content/uploads/2011/08/giemsa.pdf

142. http://himedialabs.com/TD/TC232.pdf

143. Barcia J.J. The Giemsa stain: its history and applications. Int. J. Surg. Pathol. 15, 2007,

292-296.

144. Monzote L., Cuesta-Rubio O., Fernandez M.C., Hernandez I.M., Fraga J., Perez K.,

Kerstens M., Maes L., Cos P. In vitro antimicrobial assessment of Cuban propolis

extracts. Mem Inst Oswaldo Cruz 107, 2012, 978-984.

145. Albericio F. Developments in peptide and amide synthesis. Curr. Opin. Chem. Biol. 8,

2004, 211-221.

146. Chandrudu S., Simerska P., Toth I. Chemical methods for peptide and protein production.

Molecules 18, 2013, 4373-4388.


16

147. Wittrup K.D. Disulfide bond formation and eucaryotic secretory productivity. Curr.

Opin. Biotechnol. 6, 1995, 203-208.

148. Kent S.B.H., Mitchell A.R., Engelhard M., Merrifield R.B. Mechanisms and prevention

of trifluoroacetylation in solid-phase peptide synthesis. Proc. Natl. Acad. Sci. USA 76,

1979, 2180-2184.

149. Neurath H. The proteins composition, structure, and functions V I. New York, Academic

Press INC., 1966.

150. Mant C.T., Chen Y., Yan Z., Popa T.V., Kovacs J.M., Mills J.B., Tripet B.P., Hodges

R.S. HPLC analysis and purification of peptides. Methods Mol. Biol. 386, 2007, 3-55.

151. Jeong J., Jung Y., Na S., Jeong J., Lee E., Kim M., Choi S., Shin D., Paek E., Lee H., Lee

K. Novel oxidative modifications in redox-active cysteine residues. Mol. Cell Proteomics

10, 2011, No. doi: 10.1074/mcp.M110.000513.

152. Savary B.J., Vasu P. Routine identity confirmation of recombinant proteins by MALDI-

TOF mass spectrometry. Methods Mol. Biol. 824, 2012, 37-50.

153. Koszałka P., Kamysz E., Wejda M., Kamysz W., Bigda J. Antitumor activity of

antimicrobial peptides against U937 histiocytic cell line. Acta Biochim. Pol. 58, 2011,

111-117.

154. Huang Y., He L., Li G., Zhai N., Jiang H., Chen Y. Role of helicity of -helical

antimicrobial peptides to improve specifity. Protein Cell. 5, 2014, 631-642.

155. Abbassi F., Raja Z., Oury B., Gazanion E., Piesse C., Sereno D., Nicolas P., Foulon T.,

Ladram A. Antibacterial and leishmanicidal activities of temporin – SHd, a 17-residue

long membrane-damaging peptide. Biochimie 95, 2013, 388-399.

156. Matsuzaki K. Control of cell selectivity of antimicrobial peptides. Biochim. Biophys. Acta

1788, 2009, 1687-1692.

157. Tam J.P., Wu C., Yang J.L. Membranolytic selectivity of cysteine-stabilized cyclic

protegrins. Eur. J. Biochem. 267, 2000, 3289-3300.

158. Rivas L., Luque-Ortega J.R., Andreu D. Amphibian antimicrobial peptides and Protozoa:

Lessons from parasites. Biochim. Biophys. Acta 1788, 2009, 1570-1581.

159. Pink R., Hudson A., Mouriès M.A., Bendig M. Opportunities and challenges in

antiparasitic drug discovery. Nat. Rev. Drug Discov. 4, 2009, 727-740.

160. Bell A. Antimalarial peptides: The long and the short of it. Curr. Pharm. Des. 17, 2011,

2719-2731.

161. Takeshima K., Chikushi K.K.L., Yonehara S., Matsuzaki K. Translocation of analogues

of the antimicrobial peptides magainin and buforin across human cel membranes. J. Biol.

Chem. 278, 2003, 1310-1315.


17

162. Rousselle C., Clair P., Lefauconnier J.M., Kaczorek M., Scherrmann J.M., Temsamani J.

New advances in the transport of doxorubicin through the blood-brain barrier by a peptide

vector-mediated strategy. Mol. Pharmacol. 57, 2000, 679-686.

163. Vermeer L.S., Lan Y., Abbate V., Ruh E., Bui T.T., Wilkinson L.J., Kanno T.,

Jumagulova E., Kozlowska J., Patel J., McIntyre C.A., Yam W.C., Siu G., Atkinson A.,

Lam J.K.W., Bansal S.S., Drake A.F., Mitchell G.H., Mason A.J. Conformational

flexibility determines selectivity and antibacterial, antiplasmodial, and anticancer potency

of -helical peptides. J. Biol. Chem. 287, 2012, 34120-34133.

164. Kückelhaus S.A., Leite J.R.., Muniz-Junqueira M.I., Sampaio R.N., Bloch Jr. C., Tosta

E.C. Antiplasmodial and antileishmanial activities of phylloseptin-1, an antimicrobial

peptide from the skin secretion of Phyllomedusa azurea (Amphibia). Exp. Parasitol. 123,

2009, 11-16.

165. Radzishevsky I., Krugliak M., Ginsburg H., Mor A. Antiplasmodial activity of lauryl-

lysine oligomers. Antimicrob. Agents Chemother. 51, 2007, 1753-1759.

166. Alawadi D.Y., Saadeh H.A., Kaur H., Goyal K., Sehgal R., Hadda T.B., ElSawy N.A.,

Mubarak M.S. Metronidazol derivatives as a new class of antiparasitic agents: synthesis,

prediction of biological activity, and molecular properties. Med. Chem. Res. 23, 2014, art.

No doi: 10.1007/s00044-014-1197-4.

167. Fieck A., Hurwitz I., Kang A.S., Durvasula R. Trypanosoma cruzi: synergistic

cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential

bacterial hosts. Exp. Parasitol. 125, 2010, 342-347.

168. Huang C.M., Chen H.C., Zierdt C.H. Magainin analogs effective against pathogenic

protozoa. Antimicrob. Agents Chemother. 34, 1990, 1824-1826.

169. Björn C., Håkansson J., Myhrman E., Sjöstrand V., Haug T., Lindgren K., Blencke H.M.,

Stensvåg K., Mahlapuu M. Anti-infectious and anti-inflammatory effects of peptide

fragments sequentially derived from the antimicrobial peptide centrocin 1 isolated from

the green sea urchin, Strongylocentrotus droebachiensis. AMB Express. 13, 2012, art. No

doi: 10.1186/2191-0855-2-67.

170. Leite J.R., Silva L.P., Rodrigues M.I., Prates M.W., Brand G.D., Lacava B.M., Azevedo

R.B., Bocca A.L., Albuquerque S., Bloch C Jr. Phylloseptins: a novel class of anti-

bacterial and anti-protozoan peptides from the Phyllomedusa genus. Peptides 26, 2005,

565-573.

171. Pinto E.G., Pimenta D.C., Antoniazzi M.M., Jared C., Tempone A.G. Antimicrobial

peptides isolated from Phyllomedusa nordestina (Amphibia) alter the permeability of

plasma membrane of Leishmania and Trypanosoma cruzi. Exp. Parasitol. 135, 2013,

655-660.

172. Harrington J.M., Widener J., Stephens N., Johnson T., Francia M., Capewell P., Macleod

A., Hajduk S.L. The plasma membrane of bloodstream-form African trypanosomes


18

confers susceptibility and specificity to killing by hydrophobic peptides. J. Biol. Chem.

285, 2010, 28659-28666.

173. Wędrychowicz H. Sposoby unikania skutków odpowiedzi immunologicznej żywiciela

wykorzystywane przez pasożyty. KOSMOS 54, 2005, 39-48.

174. Harrington J.M. Antimicrobial peptide killing of African Trypanosomes. Parasite

Immunol. 33, 2011, 461-469.

175. Nwaka S., Besson D., Ramirez B., Maes L., Matheeussen A., Bickle Q., Mansour N.R.,

Yousif F., Twonson S., Gokool S., Cho-Ngwa F., Samje M., Misra-Bhattacharya S.,

Murthy P.K., Fakorede F., Paris J.M., Yeates C., Ridley R., Van Voorhis W.C., Geary T.

Integrated dataset of screening hits against multiple neglected disease pathogens. PLoS

Negl. Trop. Dis. 5, 2011, art. No: doi: 10.1371/journal.pntd.0001412.

176. Andrews K.T., Fisher G., Skinner-Adams T.S. Drug repurposing and human parasitic

protozoan diseases. Int. J. Parasitol. Drugs Drug Resist. 24, 2014, 95-111.

177. Kulkarni M.M., McMaster W.R., Kamysz E., Kamysz W., Engman D.M., McGwire B.S.

The major surface-metalloprotease of the parasitic protozoa, Leishmania, protects against

antimicrobial peptide-induced apoptotic killing. Mol. Microbiol. 62, 2006, 1484-1497.

178. Kulkarni M.M., Karafova A., Kamysz W., McGwire B.S. Design of protease-resistant

pexiganan enhances antileishmanial activity. Parasitol. Res. 113, 2014, 1971-1976.

179. McGwire B.S., Kulkarni M.M. Interactions of antimicrobial peptides with Leishmania

and trypanosomes and their functional role in host parasitism. Exp. Parasitol. 126, 2010,

397-405.

180. Mangoni M.L., Saugar J.M., Dellisanti M., Barra D., Simmaco M., Rivas L. Temporins,

small antimicrobial peptides with leishmanicidal activity. J. Biol. Chem. 280, 2005,

984-990.

181. Chadbourne F.L., Raleigh C., Ali H.Z., Denny P.W., Cobb S.L. Studies on the

antileishmanial properties of the antimicrobial peptides temporin A, B, and 1Sa. J. Pept.

Sci. 17, 2011, 751-755.

182. Brand G.D., Santos R.C., Arake L.M., Silva V.G., Veras L.M., Costa V., Costa C.H.,

Kuckelhaus S.S., Alexandre J.G., Feio M.J., Leite J.R. The skin secretion of the

amphibian Phyllomedusa nordestina: a source of antimicrobial and antiprotozoal

peptides. Molecules 18, 2013, 7058-7070.

183. Nizet V. Antimicrobial peptide resistance mechanisms of human bacterial pathogens.

Curr. Issues Mol. Biol. 8, 2006, 11-26.

184. http://www.who.int/mediacentre/news/releases/2014/amr-report/en/


19

185. Malina A., Shai Y. Conjugation of fatty acids with different lengths modulates the

antimicrobial and antifungal activity of a cationic biologically inactive peptide. Biochem.

J. 390, 2005, 695-702.

186. Laverty G., Gilmore B. Cationic antimicrobial peptide cytotoxicity. SOJ Microbiol.

Infect. Dis. 2, 2014, art. No. doi: http://dx.doi.org/10.15226/sojmid.2014.00112.

187. Bellini A.M., Vertuani G., Cavazzini G. Antibacterial activity of the derivatives of

dehydro- and deoxy-cholic acids (author’s transl.). Ann. Sclavo. 18, 1976, 469-478.

188. Bellini A.M., Vertuani G., Quaglio M.P., Cavazzini G. Bile acid derivatives with

antimicrobial activity. Farmaco. Sci. 34, 1979, 967-978.

189. Lohan S., Cameotra S.S., Bisht G.S. Systematic study of non-natural short cationic

lipopeptides as novel broad-spectrum antimicrobial agents. Chem. Biol. Drug Des. 82,

2013, 557-566.

190. Gregoriadis G. Liposome technology: Entrapment of drugs and other materials into

liposomes V II. New York, Informa Healthcare USA, Inc., 2006.

191. Moore K.S., Wehrli S., Roder H., Rogers M., Forrest J.N. Jr, McCrimmon D., Zasloff M.

Squalamine: an aminosterol antibiotic from the shark. Proc. Natl. Acad. Sci. USA 90,

1993, 1354-1358.

192. Lara D., Feng Y., Bader J., Savage P.B., Maldonado R.A. Anti-trypanosomatid activity of

ceragenins. J. Parasitol. 96, 2010, 638-642.

193. Epand R.F., Savage P.B., Epand R.M. Bacterial lipid composition and the antimicrobial

efficacy of cationic steroid compounds (ceragenins). Biochim. Biophys. Acta. 1768, 2007,

2500-2509.

194. Epand R.M., Epand R.F., Savage P.B. Ceragenins (cationic steroid compounds), a novel

class of antimicrobial agents. Drug News Perspect. 21, 2008, 307-311.

195. Savage P.B., Li C., Taotafa U., Ding B., Guan Q. Antibacterial properties of cationic

steroid antibiotics. FEMS Microbiol. Lett. 217, 2002, 1-7.

196. Wade D., Silberring J., Soliymani R., Heikkinen S., Kilpeläinen I., Lankinen H., Kuusela

P. Antibacterial activities of temporin A analogs. FEBS Lett. 479, 2000, 6-9.

197. Kamysz W., Nadolski P. Przeciwbakteryjna aktywność peptydów ze skóry płazów. Ann.

Acad. Med. Gedan. 35, 2005, 29-34.

198. Cardoso M.H., Cobacho N.B., Cherobim M.D., Pinto M.F.C., Santos C., Maximiano

M.R., de Barros E.G., Dias S.C., Franco O.L. Insights into the antimicrobial activities of

unusual antimicrobial peptide families from amphibian skin. J. Clin. Toxicol. 4, 2014, art.

No. doi: 10.4172/2161-0495.1000205.


20

199. Ge Y., MacDonald D.L., Holroyd K.J., Thornsberry C., Wexler H., Zasloff M. In vitro

antibacterial properties of pexiganan, an analog of magainin. Antimicrob. Agents

Chemother. 43, 1999, 782-788.

200. Mosca D.A., Hurst M.A., So W., Viajar B.S., Fujii C.A., Falla T.J. IB-367, a protegrin

peptide with in vitro and in vivo activities against the microflora associated with oral

mucositis. Antimicrob. Agents Chemother. 44, 2000, 1803-1808.

201. Barańska-Rybak W., Cirioni O., Dawgul M., Sokołowska-Wojdyło M., Naumiuk L.,

Szczerkowska-Dobosz A., Nowicki R., Roszkiewicz J., Kamysz W. Activity of

antimicrobial peptides and conventional antibiotics against superantigen positive

Staphylococcus aureus isolated from the patients with neoplastic and inflammatory

erythrodermia. Chemother. Res. Pract. 2011, 2011, art. No doi: 10.1155/2011/270932.

202. Mangoni M.E., Aumelas A., Charnet P., Roumestand C., Chiche L., Despaux E., Grassy

G., Calas B., Chavanieu A. Change in membrane permeability induced by protegrin 1:

implication of disulphide bridges for pore formation. FEBS Lett. 383, 1996, 93-8.

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