These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.
Pubmed for Handhelds
PUBMED FOR HANDHELDS
Search MEDLINE/PubMed
Title: Structure-function study and anti-HIV activity of synthetic peptide analogues derived from viral chemokine vMIP-II. Author: Luo Z, Fan X, Zhou N, Hiraoka M, Luo J, Kaji H, Huang Z. Journal: Biochemistry; 2000 Nov 07; 39(44):13545-50. PubMed ID: 11063591. Abstract: The viral macrophage inflammatory protein II (vMIP-II) shows a broad spectrum interaction with both CC and CXC chemokine receptors including CCR5 and CXCR4, two principal coreceptors for the cellular entry of human immunodeficiency virus type 1 (HIV-1). Recently, we have shown that a synthetic peptide derived from the N-terminus of vMIP-II, designated as V1, is a potent antagonist of CXCR4 but not CCR5 [Zhou, N., et al. (2000) Biochemistry 39, 3782-3787]. In this study, we synthesized a series of new peptides derived from other regions of vMIP-II and characterized their binding activities with both CXCR4 and CCR5. The results provided further support for the notion that the N-terminus of vMIP-II is the major determinant for CXCR4 recognition and that vMIP-II probably interacts with other chemokine receptors such as CCR5 with different sequence and conformational determinants. To understand the structure-function relationship of V1 peptide, its solution conformation was studied using circular dichroism spectroscopy, which showed a random conformation similar to that of the corresponding N-terminus in native vMIP-II. In addition, we synthesized a series of mutant analogues of V1 containing alanine, glycine, or phenylalanine substitution at various positions. Residues Val-1, Arg-7, and Lys-9 of V1 peptide were found to be critical for receptor interaction, because single alanine replacement at these positions dramatically decreased peptide binding to CXCR4. In contrast, alanine or phenylalanine substitution at Cys-11 led to significant enhancement in peptide affinity for CXCR4. Finally, we showed that V1 peptide inhibits HIV-1 replication in CXCR4(+) T-cell lines. These studies provide new insights into the structure-function relationship of V1 peptide and demonstrate that this peptide may be a lead for the development of therapeutic agents.[Abstract] [Full Text] [Related] [New Search]