related to degree

• Capps, Kevin J, Ph.D. in Chemistry, Scripps Research 2000 - 2005

authors

• Capps, Kevin J
• Humiston, J.
• Dominique, R.
• Hwang, I.
• Boger, Dale

publication date

• 2005

journal

• Bioorganic & Medicinal Chemistry Letters  Journal

abstract

• The discovery of a new class of aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) inhibitors through screening peptidomimetic libraries (>40,000 compounds) that act by inhibiting requisite enzyme dimerization is disclosed. In addition to defining key structural features of the lead compounds responsible for the activity, kinetic analysis of the remarkably small inhibitors established that they act as noncompetitive, dissociative inhibitors of AICAR Tfase with the prototypical lead (A1B3, Cappsin 1) exhibiting a K(i) of 3.1 +/- 0.3 microM. Thus, the studies define a unique approach to selectively targeting AICAR Tfase over all other folate-dependent enzymes, and it represents only one of a few enzymes for which inhibition achieved by disrupting requisite enzyme dimerization has emerged from screening unbiased combinatorial libraries.

subject areas

• Dimerization
• Enzyme Inhibitors
• Hydroxymethyl and Formyl Transferases
• Kinetics
• Phosphoribosylaminoimidazolecarboxamide Formyltransferase

International Standard Serial Number (ISSN)

• 0960-894X

Digital Object Identifier (DOI)

• 10.1016/j.bcml.2005.03.094

PubMed ID

• 15911265

start page

• 2840

end page

• 2844

volume

• 15

issue

• 11