title: 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.
abstract: The constrained a-helical structure of a C-peptide is useful for enhancing anti-HIV-1 activity. The i and i+3 positions in an a-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 a-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 a-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.
authors.affiliation: Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, PO Box 115, Yusong, Daejeon 305-600, Korea. mklee@kribb.re.kr
authors.forename: Myung Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Lee
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Hahm
authors.forename: Kil Lyong
authors.initials: KL
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D004220:Disulfides; D015700:HIV Envelope Protein gp41; D010455:Peptides; D003545:Cysteine