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3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods.
Bioorg Med Chem. 2006 Mar 01; 14(5):1483-96.BM

Abstract

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 beta5 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.

Authors+Show Affiliations

Zhu YQ
School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.
Pei JF
No affiliation info available
Liu ZM
No affiliation info available
Lai LH
No affiliation info available
Cui JR
No affiliation info available
Li RT
No affiliation info available

MeSH

AldehydesBinding SitesCatalysisComputer SimulationDatabases, FactualEnzyme InhibitorsHumansLigandsModels, MolecularOligopeptidesProteasome Endopeptidase ComplexProteasome InhibitorsQuantitative Structure-Activity Relationship

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16256351

Citation

Zhu, Yong-Qiang, et al. "3D-QSAR Studies On Tripeptide Aldehyde Inhibitors of Proteasome Using CoMFA and CoMSIA Methods." Bioorganic & Medicinal Chemistry, vol. 14, no. 5, 2006, pp. 1483-96.
Zhu YQ, Pei JF, Liu ZM, et al. 3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods. Bioorg Med Chem. 2006;14(5):1483-96.
Zhu, Y. Q., Pei, J. F., Liu, Z. M., Lai, L. H., Cui, J. R., & Li, R. T. (2006). 3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods. Bioorganic & Medicinal Chemistry, 14(5), 1483-96.
Zhu YQ, et al. 3D-QSAR Studies On Tripeptide Aldehyde Inhibitors of Proteasome Using CoMFA and CoMSIA Methods. Bioorg Med Chem. 2006 Mar 1;14(5):1483-96. PubMed PMID: 16256351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3D-QSAR studies on tripeptide aldehyde inhibitors of proteasome using CoMFA and CoMSIA methods. AU - Zhu,Yong-Qiang, AU - Pei,Jian-Feng, AU - Liu,Zhen-Ming, AU - Lai,Lu-Hua, AU - Cui,Jing-Rong, AU - Li,Run-Tao, Y1 - 2005/10/26/ PY - 2005/08/05/received PY - 2005/09/30/revised PY - 2005/10/01/accepted PY - 2005/11/1/pubmed PY - 2006/5/4/medline PY - 2005/11/1/entrez SP - 1483 EP - 96 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 14 IS - 5 N2 - 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 beta5 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. SN - 0968-0896 UR - https://www.unboundmedicine.com/medline/citation/16256351/3D_QSAR_studies_on_tripeptide_aldehyde_inhibitors_of_proteasome_using_CoMFA_and_CoMSIA_methods_ DB - PRIME DP - Unbound Medicine ER -