Chemogenomics with Peptide Secondary Structure Mimetics

Title: Chemogenomics with Peptide Secondary Structure Mimetics

Volume: 6 Issue: 7

Author(s): Masakatsu Eguchi, Michael McMillan, Cu Nguyen, Jia-Ling Teo, Emil Y. Chi, William R. Henderson Jr. and Michael Kahn

Affiliation:

Keywords: chemogenomics, peptide secondary, structure mimetics, activator protein-1, nuclear factor kappa b, human thioredoxin

Abstract: There is increasing evidence that redox regulation of transcription, particularly activator protein-1 (AP-1) and nuclear factor kappa B (NF-kB), is important in inflammatory diseases. Human thioredoxin (TRX), a member of the oxidoreductase superfamily, was initially identified, as a factor which augments the production of interleukin-2 receptor alpha (IL-2R α) in human T-cell lymphotropic virus type 1 (HTLV-1) infected patient T-cells. Substrates for the redox activity of TRX bind the active site cleft in extended strand structure. The rapid generation of high numbers of peptide secondary structure mimetics through solid-phase synthesis is a key technology for the identification of pharmaceutical leads based on such protein-peptide interactions. In this manuscript, we describe a chemogenomic approach utilizing an extended strand templated library to develop small molecule inhibitors to validate oxidoreductase molecular targets in a murine asthma model.

Cite this article as:

Eguchi Masakatsu, McMillan Michael, Nguyen Cu, Teo Jia-Ling, Chi Y. Emil, Henderson Jr. R. William and Kahn Michael, Chemogenomics with Peptide Secondary Structure Mimetics, Combinatorial Chemistry & High Throughput Screening 2003; 6 (7) . https://dx.doi.org/10.2174/138620703771981197