中国化学快报(英文版)2024，Vol.35Issue(3) ：384-388.DOI:10.1016/j.cclet.2023.108530

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

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
中国化学快报(英文版)2024，Vol.35Issue(3) ：384-388.DOI:10.1016/j.cclet.2023.108530
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Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin

Yi-Jing Li 1Lingze Zhang 2Ming-Hao Pang 3Pei-Pei Yang 2Lu-Ming Guo 2Kuo Zhang 2Da-Yong Hou 2Lei Wang 2Hao Wang 2Hui Cao3
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作者信息

  • 1. State Key Laboratory for Advanced Metals and Materials,School of Materials Science and Engineering,University of Science and Technology Beijing,Beijing 100083,China;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
  • 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
  • 3. State Key Laboratory for Advanced Metals and Materials,School of Materials Science and Engineering,University of Science and Technology Beijing,Beijing 100083,China
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Abstract

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(KD)of ABPs to albumin is up to 1 x 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.

Key words

One-bead one-compound/Combinatorial library/Albumin binding/Drug delivery/Triptorelin

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基金项目

国家自然科学基金(51890891)

国家自然科学基金(51890894)

国家自然科学基金(52073027)

国家自然科学基金(51773017)

国家重点研发计划(2018YFE0205400)

中央高校基本科研业务费专项(FRF-DF-19-001)

出版年

2024
中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
参考文献量47
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