Ionic immobilization, diversification, and release: Application to the generation of a library of methionine aminopeptidase inhibitors

Punitha Vedantham, Jennifer M. Guerra, Frank Schoenen, Min Huang, Parul J. Gor, Gunda I. Georg, Jenna L. Wang, Benjamin Neuenswander, Gerald H. Lushington, Lester A. Mitscher, Qi Zhuang Ye, Paul R. Hanson

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Development of an ionic immobilization, diversification, and release method for the generation of methionine aminopeptidase inhibitors is reported. This method involves the immobilization of 5-bromofuran-2-carboxylic acid and 5-bromothiophene-2-carboxylic acid onto PS-BEMP, followed by Suzuki reaction on a resinbound intermediate and subsequent release to provide products in moderate yields and excellent purities. Compound potencies were evaluated on the Co(II), Mn(II), Ni(II), and Fe(II) forms of Escherichia coli MetAP1. The furoic-acid analogs were found to be Mn(II) selective with IC50 values in the low micromolar range. Qualitative SAR analysis, supplemented by molecular modeling studies, provides valuable information on structural elements responsible for potency and selectivity.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalJournal of Combinatorial Chemistry
Volume10
Issue number2
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Chemistry(all)

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    Vedantham, P., Guerra, J. M., Schoenen, F., Huang, M., Gor, P. J., Georg, G. I., Wang, J. L., Neuenswander, B., Lushington, G. H., Mitscher, L. A., Ye, Q. Z., & Hanson, P. R. (2008). Ionic immobilization, diversification, and release: Application to the generation of a library of methionine aminopeptidase inhibitors. Journal of Combinatorial Chemistry, 10(2), 185-194. https://doi.org/10.1021/cc700085c