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Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin
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作者 Yi-Jing Li Lingze Zhang +7 位作者 Ming-Hao Pang Pei-Pei Yang Lu-Ming Guo Kuo Zhang Da-Yong Hou Lei Wang Hao Wang Hui Cao 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第3期384-388,共5页
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 circulatio... 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. 展开更多
关键词 One-bead one-compound Combinatorial library Albumin binding Drug delivery TRIPTORELIN
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Functional Peptides from One-bead One-compound High-throughput Screening Technique 被引量:1
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作者 YAN Yaqiong WANG Lei WANG Hao 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2023年第1期83-91,共9页
Combinatorial chemistry provides a cost-effective method for the rapid discovery of new functional peptides.One-bead one-compound(OBOC)high-throughput screening technique offers a lot of structurally diverse peptides ... Combinatorial chemistry provides a cost-effective method for the rapid discovery of new functional peptides.One-bead one-compound(OBOC)high-throughput screening technique offers a lot of structurally diverse peptides to be rapidly synthesized and screened for binding to a target of interest.The OBOC peptide library screening involves three main steps:library construction,positive beads separation,and peptide sequencing.This review mainly summarizes some special technique tips during functional peptide screening and potential future directions of the OBOC high-throughput screening technique. 展开更多
关键词 Combinatorial chemistry One-bead one-compound(OBOC) Cyclic peptide Peptide screening Self-assembly
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Chemical protein synthesis-assisted high-throughput screening strategies for D-peptides in drug discovery 被引量:1
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作者 Ying Li Xiuxiu Cao +1 位作者 Changlin Tian Ji-Shen Zheng 《Chinese Chemical Letters》 SCIE CAS CSCD 2020年第9期2365-2374,共10页
D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and spe... D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One D-peptide etelcalcetide has even entered the market that targets the calcium(Ca2+)-sensing receptor(CaSR) to fight secondary hyperparathyroidism.Effective discovery and optimization of D-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of D-peptide drugs.This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for D-peptide ligands and their application in drug discovery. 展开更多
关键词 Chemical protein synthesis Mirror-image proteins Mirror-image phage display Mirror-image one-bead one-compound(OBOC) D-Peptide drug
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