从噬菌体展示随机肽库中定量筛选人血清白蛋白黏附肽

Quantitative screening human serum albumin binding peptides using phage display random peptide library

人血清白蛋白作为长效化载体蛋白可用于改善蛋白质药物的半衰期。除了以人血清白蛋白融合方式提高蛋白质药物的半衰期,黏附人血清白蛋白也已成为改善蛋白质药物药代动力学特性的策略。本研究以人血清白蛋白为靶分子,利用噬菌体表面展示技术对随机七肽库进行生物淘选,挑取噬菌体单克隆进行特异性鉴定。经4轮生物淘选后回收率和选择比都有了一定提高,使用滴度检测方法对所挑选的噬菌体阳性克隆进行了相对亲和力的测定,并经过DNA测序得到了4个特异性黏附肽HSA-1、HSA-5、HSA-6和HSA-10的序列。将此类多肽插入到蛋白质药物上,将有助于提高蛋白质药物在血清中的半衰期,从而达到长效目的。

Human serum albumin（HSA） is a long-acting carrier protein in drug design for prolonging the half-lives of protein drugs.Not only HSA fusion protein but also HSA binding protein has become general strategy for improving the pharmacokinetics of proteins.Using Ph.D.-7 phage display random peptide library,we identified a series of peptides that specially bind to HSA.The recovery yield and specificity ratio have been defined as the selection criteria in the panning process.After 4 rounds selection,the recovery yield and specificity ratio of human albumin binding peptide are both having a certain increase.The relative affinities of the four individual clones were assayed with the method of the measurement of phage titres.Four HSA binding peptides HSA-1,HSA-5,HSA-6 and HSA-10 were also characterized by DNA sequencing,which were inserted into the protein drugs to prolong their half-lives in the serum.