title: Chemogenomics with peptide secondary structure mimetics.
abstract: There is increasing evidence that redox regulation of transcription, particularly activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB), 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 alpha) 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.
authors.affiliation: Pacific Northwest Research Institute, Seattle, Washington 98122, USA.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Eguchi
authors.forename: Michael
authors.initials: M
authors.lastname: McMillan
authors.forename: Cu
authors.initials: C
authors.lastname: Nguyen
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Teo
authors.forename: Emil Y
authors.initials: EY
authors.lastname: Chi
authors.forename: William R
authors.initials: WR
authors.lastname: Henderson
authors.forename: Michael
authors.initials: M
authors.lastname: Kahn
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D019151:Peptide Library; D010455:Peptides; D043562:Receptors, G-Protein-Coupled