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, Qizhuang Ye, Paul R. Hanson

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Aminopeptidases
Diversification
Carboxylic Acids
Immobilization
Methionine
Inhibitor
Molecular Modeling
Molecular modeling
Selectivity
Escherichia coli
Escherichia Coli
Inhibitory Concentration 50
Analogue
Acids
Range of data
Libraries
Form

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Discrete Mathematics and Combinatorics

Cite this

Ionic immobilization, diversification, and release : Application to the generation of a library of methionine aminopeptidase inhibitors. / Vedantham, Punitha; Guerra, Jennifer M.; Schoenen, Frank; Huang, Min; Gor, Parul J.; Georg, Gunda I.; Wang, Jenna L.; Neuenswander, Benjamin; Lushington, Gerald H.; Mitscher, Lester A.; Ye, Qizhuang; Hanson, Paul R.

In: Journal of Combinatorial Chemistry, Vol. 10, No. 2, 03.2008, p. 185-194.

Research output: Contribution to journalArticle

Vedantham, P, Guerra, JM, Schoenen, F, Huang, M, Gor, PJ, Georg, GI, Wang, JL, Neuenswander, B, Lushington, GH, Mitscher, LA, Ye, Q & Hanson, PR 2008, 'Ionic immobilization, diversification, and release: Application to the generation of a library of methionine aminopeptidase inhibitors', Journal of Combinatorial Chemistry, vol. 10, no. 2, pp. 185-194. https://doi.org/10.1021/cc700085c
Vedantham, Punitha ; Guerra, Jennifer M. ; Schoenen, Frank ; Huang, Min ; Gor, Parul J. ; Georg, Gunda I. ; Wang, Jenna L. ; Neuenswander, Benjamin ; Lushington, Gerald H. ; Mitscher, Lester A. ; Ye, Qizhuang ; Hanson, Paul R. / Ionic immobilization, diversification, and release : Application to the generation of a library of methionine aminopeptidase inhibitors. In: Journal of Combinatorial Chemistry. 2008 ; Vol. 10, No. 2. pp. 185-194.
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