1. Effects of cathelicidin and its fragments on three key enzymes of HIV-1.
- Author
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Wong JH, Legowska A, Rolka K, Ng TB, Hui M, Cho CH, Lam WW, Au SW, Gu OW, and Wan DC
- Subjects
- Anti-HIV Agents pharmacology, Dose-Response Relationship, Drug, Escherichia coli, Female, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, HIV Infections virology, HIV Integrase genetics, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV Reverse Transcriptase metabolism, HeLa Cells, Humans, Inhibitory Concentration 50, Kinetics, Leukocytes, Mononuclear drug effects, Plasmids, Protein Binding, Surface Plasmon Resonance, Transfection, Cathelicidins, Antimicrobial Cationic Peptides pharmacology, Green Fluorescent Proteins antagonists & inhibitors, HIV Infections enzymology, HIV Integrase metabolism, HIV Protease metabolism, HIV Reverse Transcriptase antagonists & inhibitors, HIV-1 drug effects, HIV-1 enzymology, Peptide Fragments pharmacology
- 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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