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Phenylbutazone, a New Long‐Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier
Author(s) -
Zhou Jie,
Li Xue,
Zhu Xiaoyun,
Sun Jian,
Qiu Qianqian,
Huang Wenlong,
Qian Hai
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12726
Subject(s) - peptide yy , pharmacokinetics , agonist , phenylbutazone , chemistry , pharmacology , albumin , human serum albumin , peptide , linker , serum albumin , appetite , receptor , endocrinology , conjugate , medicine , biochemistry , neuropeptide , neuropeptide y receptor , computer science , operating system , mathematical analysis , mathematics
As a NPY ‐2 receptor agonist, PYY 24–36‐ Leu 31 is reported to suppress appetite and has a potential in obesity treatment, but its short half‐life limits the clinical application. The use of chemical modification to improve interactions with human serum albumin ( HSA ) is an effective strategy for prolonging the half‐lives of peptide analogues. So based on the characteristics that phenylbutazone has a good combination with HSA , we selected a proper linker to link with PYY 24–36 ‐Leu 31 to create long‐acting and highly biologically active PYY 24–36 ‐Leu 31 conjugates, and successfully find a novel, long‐acting PYY 24–36 ‐Leu 31 conjugate 8 that, when dosed every other day in diet induce obese ( DIO ) mice for 2 weeks, results in a significant reduction in food intake and body weight and improvement in blood parameter and hepatic steatosis.