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

doi:10.1021/cc700085c

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

Medicinal Chemistry

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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 language	English (US)
Pages (from-to)	185-194
Number of pages	10
Journal	Journal of Combinatorial Chemistry
Volume	10
Issue number	2
DOIs	https://doi.org/10.1021/cc700085c
State	Published - Mar 2008

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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

Vedantham, P, Guerra, JM, Schoenen, F, Huang, M, Gor, PJ, Georg, GI, Wang, JL, Neuenswander, B, Lushington, GH, Mitscher, LA, Ye, QZ & 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

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

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.",

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

year = "2008",

month = mar,

doi = "10.1021/cc700085c",

language = "English (US)",

volume = "10",

pages = "185--194",

journal = "Journal of Combinatorial Chemistry",

issn = "1520-4766",

publisher = "American Chemical Society",

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T1 - Ionic immobilization, diversification, and release

T2 - Application to the generation of a library of methionine aminopeptidase inhibitors

AU - Vedantham, Punitha

AU - Guerra, Jennifer M.

AU - Schoenen, Frank

AU - Huang, Min

AU - Gor, Parul J.

AU - Georg, Gunda I.

AU - Wang, Jenna L.

AU - Neuenswander, Benjamin

AU - Lushington, Gerald H.

AU - Mitscher, Lester A.

AU - Ye, Qi Zhuang

AU - Hanson, Paul R.

PY - 2008/3

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AB - 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.

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JO - Journal of Combinatorial Chemistry

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ER -

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

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