Open Accessα/Sulfono-γ-AApeptide Hybrid Analogues of Glucagon with Enhanced Stability and Prolonged In Vivo Activity
Author(s) -
Peng Sang,
Hongxiang Zeng,
Candy Lee,
Yan Shi,
Minghui Wang,
Cong Pan,
Lulu Wei,
ChengLong Huang,
MeiHwan Wu,
Weijun Shen,
Xi Li,
Jianfeng Cai
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c01289
Subject(s) - chemistry , in vivo , metabolic stability , peptide , bioavailability , pharmacology , glucagon , biochemistry , drug , biological activity , in vitro , hormone , medicine , biology , microbiology and biotechnology
Peptide drugs have the advantages of target specificity and good drugability and have become one of the most increasingly important hotspots in new drug research in biomedical sciences. However, peptide drugs generally have low bioavailability and metabolic stability, and therefore, the modification of existing peptide drugs for the purpose of improving stability and retaining activity is of viable importance. It is known that glucagon is an effective therapy for treating severe hypoglycemia, but its short half-life prevents its wide therapeutic use. Herein, we report that combined unnatural residues and long fatty acid conjugation afford potent α/sulfono-γ-AApeptide hybrid analogues of Glucagon with enhanced stability and prolonged in vivo activity. This strategy could be adopted to develop stabilized analogues of other short-acting bioactive peptides.