Screening and identification of HIV-1 gp41 C-helix mimotopes displayed on phages / 中国免疫学杂志

ABSTRACT

Objective:To find small molecular leads for inhibition on early stage of HIV infection by identification and characterization of the HIV-1 gp41 C-helix mimotopes.Methods:For identification of the gp41 C-helix mimotopes,C7C phage display peptide library was biopanning by using a synthetic peptide N36 which was derived from the gp41 N-helix as target.After three rounds of screening,positive phage clones were identified by ELISA and sequenced.Results:16 of 26 phage clones were identified to bind with peptide N36,and 10 of them were sequenced.Every clone of ten clones contains at least two hydrophobic residues,which may dock into the hydrophobic pocket in the gp41 N-helix domain.9 of the 10 clones have a conservative sequence WW,which may mimic the W628 and W631 in C-helix to interact with the hydrophobic residues in the gp41 pocket.One clone expressing the conservative sequence named clone No.8(CYWWHRLHC) was selected for characterization.The binding between the clone No.8 and N36 was blocked by free peptide N36.And the binding between clone No.8 and peptide N36 was inhibited by peptide C34(IC 50=12.5 ?g/ml).Conclusion:The short circular peptides displayed on phages containing WW residues may mimic the conformational epitope of the HIV-1 gp41 C-helix to interact with the N-helix.This information may be useful for design of HIV-1 fusion inhibitors.