3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using   CoMFA and CoMSIA methods

doi:10.1016/j.bmc.2005.10.003

CORC > 北京大学 > 化学与分子工程学院

	3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods
	Zhu, YQ ; Pei, JF ; Liu, ZM ; Lai, LH ; Cui, JR ; Li, RT
刊名	生物有机化学与医药化学
	2006
关键词	3D-QSAR CoMFA CoMSIA proteasome inhibitors tripeptide aldehyde drug design MULTICATALYTIC PROTEINASE COMPLEX MOLECULAR SIMILARITY INDEXES CHYMOTRYPSIN-LIKE ACTIVITY 20S PROTEASOME BETA-SUBUNITS SELECTIVE INHIBITORS ANTIGEN PRESENTATION PROTEOLYTIC SYSTEM 26S PROTEASOME FIELD ANALYSIS
DOI	10.1016/j.bmc.2005.10.003
英文摘要	The ubiquitin-proteasome pathway plays a crucial role in the regulation of many physiological processes and in the development of a number of major human diseases, such as cancer, Alzheimer's, Parkinson's, diabetes, etc. As a new target, the study on the proteasome inhibitors has received much attention recently. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies using comparative molecule field analysis (CoMFA) and comparative molecule similarity indices analysis (CoMSIA) techniques were applied to analyze the binding affinity of a set of tripeptide aldehyde inhibitors of 20S proteasome. The optimal CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q(2)) of 0.615, 0.591 and conventional coefficients (r(2)) of 0.901, 0.894, respectively. These models were validated by a test set of eight molecules that were not included in the training set. The predicted correlation coefficients (r(2)) of CoMFA and CoMSIA are 0.944 and 0.861, respectively. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of beta 5 subunit of 20S proteasome, which suggests that the 3D-QSAR models built in this paper can be used to guide the development of novel inhibitors of 20S proteasome. (c) 2005 Elsevier Ltd. All rights reserved.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000235244400020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic; SCI(E); PubMed; 16; ARTICLE; 5; 1483-1496; 14
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/199042]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Zhu, YQ,Pei, JF,Liu, ZM,et al. 3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods[J]. 生物有机化学与医药化学,2006.
APA	Zhu, YQ,Pei, JF,Liu, ZM,Lai, LH,Cui, JR,&Li, RT.(2006).3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods.生物有机化学与医药化学.
MLA	Zhu, YQ,et al."3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods".生物有机化学与医药化学 (2006).