Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding

Theranostics
Haojun ChenXiaoyuan Chen

Abstract

The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs.

Citations

Dec 8, 2015·Bioconjugate Chemistry·Yi LiuXiaoyuan Chen
Jun 22, 2016·Advanced Drug Delivery Reviews·Xiaolian SunXiaoyuan Chen
May 11, 2017·Drug Development and Industrial Pharmacy·Shiva GolmohammadzadehBahman Khameneh
Oct 10, 2018·Advanced Healthcare Materials·Gang NiuXiaoyuan Chen
Jul 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Samantha M SarettCraig L Duvall
Apr 7, 2019·Nature Biomedical Engineering·Peng ZhaoMingnan Chen
Mar 30, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Eugene V GolanovGavin W Britz
Jun 1, 2018·Contrast Media & Molecular Imaging·Linpeng YaoFeng Chen
Jan 8, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Yesen LiZhen Cheng
Jun 15, 2019·Biomolecules·Alessandro ParodiAndrey A Zamyatnin
Jul 1, 2020·ACS Applied Materials & Interfaces·Shuaijian NiGe Zhang
Feb 3, 2018·Advanced Drug Delivery Reviews·Wei ChenXiaoyuan Chen
May 15, 2021·Journal of Pharmaceutical Sciences·Farrukh ZeeshanPrashant Kesharwani
Nov 24, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Haojun ChenXiaoyuan Chen
Apr 13, 2018·ACS Applied Materials & Interfaces·Xiangyu WangXiaoyuan Chen

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Methods Mentioned

BETA
glycosylation

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GraphPad
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