Exp Mol Med.  2006 Feb;38(1):18-26.

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

• Lee MK
• Kim HK
• Lee TY
• Hahm KS
• Kim KL

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.

Keyword

anti-HIV agents; HIV-1; HIV envelope protein gp41; receptors; HIV; structure-activity relationship; viral fusion proteins

MeSH Terms

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