Identification of TNF-alpha inhibitors from a split-pool library based on a tyrosine-proline peptidomimetic scaffold.
The design and synthesis of a combinatorial library based on a 4-aryloxyproline scaffold with tyrosine as the aryl portion is described. The 1728 member library was prepared using the split-pool method to generate pools of compounds. Screening of the library components as mixtures followed by deconvolution led to the discovery of novel inhibitors of TNF-alpha induced apoptosis.
Jackson
Randy W
RW
Department of Chemistry, Celltech R&D, Inc., 1621 220th Street SE, Bothell, WA 98021, USA. randy.jackson@viropharma.com
Tabone
John C
JC
Howbert
J Jeffry
JJ
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry*
D007202:Indicators and Reagents; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D011392:Proline