Structure-activity relationships of anti-HIV-1 peptides with disulfide linkage between D- and L-cysteine at positions i and i+3, respectively, derived from HIV-1 gp41 C-peptide.
- Author:
Myung Kyu LEE
1
;
Hee Kyung KIM
;
Tae Young LEE
;
Kyung Soo HAHM
;
Kil Lyong KIM
Author Information
1. Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, PO Box 115, Yusong, Daejeon 305-600, Korea. mklee@kribb.re.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
anti-HIV agents;
HIV-1;
HIV envelope protein gp41;
receptors;
HIV;
structure-activity relationship;
viral fusion proteins
- MeSH:
Amino Acid Sequence;
Anti-HIV Agents/chemical synthesis/*chemistry/isolation & purification/*pharmacology;
Cell Line;
Circular Dichroism;
Cysteine/chemistry;
Disulfides/chemistry;
HIV Envelope Protein gp41/*chemistry;
HIV-1/*drug effects/growth & development;
Humans;
Inhibitory Concentration 50;
Models, Molecular;
Molecular Sequence Data;
Peptides/chemical synthesis/*chemistry/isolation & purification/*pharmacology;
Protein Structure, Secondary;
Protein Structure, Tertiary;
Research Support, Non-U.S. Gov't;
Structure-Activity Relationship
- From:Experimental & Molecular Medicine
2006;38(1):18-26
- CountryRepublic of Korea
- Language:English
-
Abstract:
The constrained alpha-helical structure of a C-peptide is useful for enhancing anti-HIV-1 activity. The i and i+3 positions in an alpha-helical structure are located close together, therefore D-Cys (dC) and L-Cys (C) were introduced at the positions, respectively, to make a dC-C disulfide bond in 28mer C-peptides. Accordingly, this study tested whether a dC-C disulfide bond would increase the alpha-helicity and anti-HIV-1 activity of peptides. A C-peptide can be divided into three domains, the N-terminal hydrophobic domain (HPD), middle interface domain (IFD), and C-terminal hydrogen domain (HGD), based on the binding property with an N-peptide. In general, the dC-C modifications in HPD enhanced the anti-HIV-1 activity, while those in IFD and HGD resulted in no or much less activity. The modified peptides with no activity clearly showed much less alpha-helicity than the native peptides, while those with higher activity showed an almost similar or slightly increased alpha-helicity. Therefore, the present results suggest that the introduction of a dC-C bridge in the N-terminal hydrophobic domain of a C-peptide may be useful for enhancing the anti-HIV-1 activity.
