The role of serum albumin in the metabolism of Boc5: Molecular identification, species differences and contribution to plasma metabolism

	The role of serum albumin in the metabolism of Boc5: Molecular identification, species differences and contribution to plasma metabolism
	Ge, Guang-Bo 1; Ai, Chun-Zhi 1; Hu, Wen-Bing 2; Hou, Jie 3; Zhu, Liang-Liang 1; He, Gui-Yuan 1; Fang, Zhong-Ze 1; Liang, Si-Cheng 1; Wang, Fu-Yi 2; Yang, Ling 1
刊名	european journal of pharmaceutical sciences
	2013-01-23
卷号	48 期号:1-2 页码:360-369
关键词	Boc5 Albumin Pseudo-esterase Transesterification Species differences
通讯作者	汪福意 ; 杨凌
产权排序	待补充
合作状况	英
英文摘要	boc5, the first nonpeptidic agonist of glucagon-like peptide-1 receptor, has been recognized as a potential candidate for treatment of diabetes. however, the metabolic behaviors of this novel molecule in both human and experimental animals remain unclear. this study aimed to explore the metabolic behaviors of boc5 in biological preparations from human, pig and rat. boc5 was found to be very stable in liver microsomes of human, pig and rat, but it can be degraded to two metabolites in plasma from all three species, via the successive hydrolysis of the c-22 esters. chemical inhibition studies using selective esterase inhibitors and assays with purified enzymes suggested that boc5 hydrolysis in human was totally mediated by human serum albumin (hsa) rather than esterases. esi-tof-ms/ms analysis revealed that lys525 of hsa could be modified by treatment with boc5, strongly suggesting the pseudo-esterase activity of albumin. studies on species differences in this albumin-mediated metabolism showed large species differences in degradation rate of boc5, the half lives of boc5 in plasma from three various species varied from 23.5 h to 83.1 h, but they were much closer to the half lives of boc5 in corresponding serum albumins, implying the predominant role of serum albumin in plasma metabolism of boc5. additionally, the effects of various ligands including fatty acids and several drugs with unambiguous binding sites on hsa, on the pseudo-esterase activity of hsa, were also investigated using both experimental and molecular modelling studies. these results showed that the binding of various ligands to hsa could significantly affect the pseudo-esterase activity of hsa towards boc5, due to the ligand-induced conformation changes of hsa. (c) 2012 elsevier b.v. all rights reserved.
学科主题	物理化学
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	pharmacology & pharmacy
研究领域[WOS]	pharmacology & pharmacy
关键词[WOS]	glucagon-like peptide-1 ; esterase-like activity ; free fatty-acids ; type-2 diabetes-mellitus ; receptor agonist ; substituted aspirins ; crystal-structures ; glycemic control ; drug discovery ; beta-cell
收录类别	SCI
资助信息	1，1
原文出处	369
语种	英语
WOS记录号	WOS:000315613500040
公开日期	2014-09-11
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/119127]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China 2.Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, Beijing 100080, Peoples R China 3.Dalian Med Univ, Dept Biotechnol, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Ge, Guang-Bo,Ai, Chun-Zhi,Hu, Wen-Bing,et al. The role of serum albumin in the metabolism of Boc5: Molecular identification, species differences and contribution to plasma metabolism[J]. european journal of pharmaceutical sciences,2013,48(1-2):360-369.
APA	Ge, Guang-Bo.,Ai, Chun-Zhi.,Hu, Wen-Bing.,Hou, Jie.,Zhu, Liang-Liang.,...&Yang, Ling.(2013).The role of serum albumin in the metabolism of Boc5: Molecular identification, species differences and contribution to plasma metabolism.european journal of pharmaceutical sciences,48(1-2),360-369.
MLA	Ge, Guang-Bo,et al."The role of serum albumin in the metabolism of Boc5: Molecular identification, species differences and contribution to plasma metabolism".european journal of pharmaceutical sciences 48.1-2(2013):360-369.