Strathprints logo
Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

Doing the methylene shuffle - further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine

Abualhasan, Murad N. and Good, James A. D. and Wittayanarakul, Kitiyaporn and Anthony, Nahoum G. and Berretta, Giacomo and Rath, Oliver and Kozielski, Frank and Sutcliffe, Oliver B. and Mackay, Simon P. (2012) Doing the methylene shuffle - further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine. European Journal of Medicinal Chemistry, 54. pp. 483-498. ISSN 0223-5234

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on these data, we have explored the SAR of the trityl head group using the methylene shuffle strategy to expand the occupation of one of the hydrophobic pockets. The most potent compounds exhibit strong (<100 nM) inhibition of Eg5 in the basal ATPase assay and inhibit growth in a variety of tumour-derived cell lines. (C) 2012 Elsevier Masson SAS. All rights reserved.

Item type: Article
ID code: 42311
Keywords: methylene shuffle , insights, inhibition, mitotic kinesin Eg5 with S-trityl L-cysteine , Pharmacy and materia medica, Organic Chemistry, Drug Discovery, Pharmacology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
Depositing user: Pure Administrator
Date Deposited: 07 Dec 2012 15:25
Last modified: 27 Mar 2014 10:45
URI: http://strathprints.strath.ac.uk/id/eprint/42311

Actions (login required)

View Item