Screening of inhibitors for influenza A virus using high-performance affinity chromatography and combinatorial peptide libraries.
The affinity inhibitor of fusion peptide of influenza A virus has been studied using a combination of high-performance affinity chromatography (HPAC) and combinatorial peptide libraries. Fusion peptide (FP) (1-11) of influenza A virus was used as the affinity ligand and immobilized onto the poly(glycidyl methacrylate) (PGMA) beads. Positional scanning peptide libraries based on antisense peptide strategy and extended peptide libraries were designed and synthesized. The screening was carried out at acidic pH (5.5) in order to imitate the environment of virus fusion. A hendecapeptide FHRKKGRGKHK was identified to have a strong affinity to the FP (1-11). The dissociation constant of the complex of the hendecapeptide and the FP (1-11) is 3.10 x 10(-6) mol l(-1) in a physiological buffer condition. The polypeptide has a fairly inhibitory effect on three different strains of influenza A virus H1N1 subtype.
Zhao
Rui
R
Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Zhong Guan Cun, Beijing 100080, China. zhaorui@iccas.ac.cn
Fanga
Canliang
C
Yu
Xiao
X
Liu
Yang
Y
Luo
Jia
J
Shangguan
Dihua
D
Xiong
Shaoxiang
S
Su
Tiansheng
T
Liu
Guoquan
G
D000595:Amino Acid Sequence; D002846:Chromatography, Affinity / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D009980:Influenza A virus / Q000187:drug effects*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology
D009842:Oligopeptides