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Chemogenomics with Peptide Secondary Structure Mimetics

[ Vol. 6 , Issue. 7 ]

Author(s):

Masakatsu Eguchi, Michael McMillan, Cu Nguyen, Jia-Ling Teo, Emil Y. Chi, William R. Henderson Jr. and Michael Kahn   Pages 611 - 621 ( 11 )

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.

Keywords:

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

Affiliation:

Department of Pathobiology, University of Washington, Seattle, Washington 98195, USA.



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