Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin  

作　　者：Yi-Jing Li Lingze Zhang Ming-Hao Pang Pei-Pei Yang Lu-Ming Guo Kuo Zhang Da-Yong Hou Lei Wang Hao Wang Hui Cao 

机构地区：[1]State Key Laboratory for Advanced Metals and Materials,School of Materials Science and Engineering,University of Science and Technology Beijing,Beijing 100083,China [2]CAS Center for Excellence in Nanoscience,CAS Key Laboratory for Biomedical Effects of Nanomaterials Nanosafety,National Center for Nanoscience and Technology(NCNST),Beijing 100190,China

出　　处：《Chinese Chemical Letters》2024年第3期384-388,共5页中国化学快报（英文版）

基　　金：supported by National Natural Science Foundation of China(Nos.51890891,51890894,52073027,and 51773017);National Key R&D Program of China(No.2018YFE0205400);the Fundamental Research Funds for the Central Universities(No.FRFDF-19–001)。

摘　　要：Peptide drugs are known for their high biological safety.However,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in half-life.Herein,inspired by the long circulation of albumin in blood,we screened albumin binding peptides(ABPs)from a one-bead one-compound(OBOC)peptide library to increase the half-life of peptide drugs.Beads displaying random peptides were screened using fluorescent labeled human serum albumin.Fluorescent beads with specific binding to albumin were isolated for sequencing.The selected ABPs can effectively bind to albumin,thus possessing the long circulation of albumin.The dissociation constant(K_(D))of ABPs to albumin is up to 1×10^(-8)mol/L.Once one of ABPs(ABP2)was coupled to triptorelin,the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone(179.07 h).In addition,the combination therapy using ABP-conjugated triptorelin and doxorubicin(DOX)can effectively inhibit the proliferation of tumor cells in mice.The OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs.

关 键 词：One-bead one-compound Combinatorial library Albumin binding Drug delivery TRIPTORELIN 

分 类 号：TQ460.1[化学工程—制药化工]