title: Effects of cathelicidin and its fragments on three key enzymes of HIV-1.
abstract: Cathelicidins exhibit anti-HIV activity but it is not known if they reduce the activity of enzymes crucial to the life cycle of the retrovirus. It is shown in this investigation that human cathelicidin LL37 and its fragments LL13-37 and LL17-32 inhibited HIV-1 reverse transcriptase dose-dependently with an IC50 value of 15μM, 7μM, and 70μM, respectively. The three peptides inhibited HIV-1 protease with a weak potency, achieving 20-30% inhibition at 100μM. The mechanism of inhibition was protein-protein interaction as revealed by surface plasmon resonance. The peptides were devoid of the ability to inhibit translocation of HIV-1 integrase, which has been labeled with green fluorescent protein, into the nucleus. The peptides did not exert toxicity on human peripheral blood mononuclear cells.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jack Ho
authors.initials: JH
authors.lastname: Wong
authors.forename: Anna
authors.initials: A
authors.lastname: Legowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rolka
authors.forename: Tzi Bun
authors.initials: TB
authors.lastname: Ng
authors.forename: Mamie
authors.initials: M
authors.lastname: Hui
authors.forename: Chi Hin
authors.initials: CH
authors.lastname: Cho
authors.forename: Wendy Wai Ling
authors.initials: WW
authors.lastname: Lam
authors.forename: Shannon Wing Ngor
authors.initials: SW
authors.lastname: Au
authors.forename: Oscar Wangang
authors.initials: OW
authors.lastname: Gu
authors.forename: David Chi Cheong
authors.initials: DC
authors.lastname: Wan
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005260:Female; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000201:enzymology* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism*; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010957:Plasmids; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D014162:Transfection; D054804:Cathelicidins
chemical_list: D019380:Anti-HIV Agents; D023181:Antimicrobial Cationic Peptides; D010446:Peptide Fragments; D049452:Green Fluorescent Proteins; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; C514801:p31 integrase protein, Human immunodeficiency virus 1; D054804:Cathelicidins