John B. Nicholas

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The identification of small molecule antagonists of protein function is at the core of the pharmaceutical industry. Successful approaches to this problem, including screening and rational design, have been developed over the years to identify antagonists of enzymes and cellular receptors. These methods have been extended to the search for inhibitors of(More)
Danoprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor that promotes multi-log(10) reductions in HCV RNA when administered as a 14-day monotherapy to patients with genotype 1 chronic HCV. Of these patients, 14/37 experienced a continuous decline in HCV RNA, 13/37 a plateau, and 10/37 a rebound. The rebound and continuous-decline groups(More)
The syntheses of potent small molecule inhibitors of the CDK2/cyclinA recruitment site are described. Structure-activity trends of nanomolar octapeptides were examined through amino-acid substitution and truncation of the sequence resulting in the identification of a smaller, albeit significantly less potent, tetrapeptide lead. These losses in affinity were(More)
The process of converting methanol to hydrocarbons on the aluminosilicate zeolite HZSM-5 was originally developed as a route from natural gas to synthetic gasoline. Using other microporous catalysts that are selective for light olefins, methanol-to-olefin (MTO) catalysis may soon become central to the conversion of natural gas to polyolefins. The mechanism(More)
Photoelectron spectra of the three isomers of the benzene dicarboxylate dianion ͑o-, m-, and p-BDC 2Ϫ ͒ were measured in the gas phase at five photon energies. Detachment features from the carboxylate groups and the ␲ electrons of the ring were clearly observed and distinguished. The electron binding energies were found to increase from the very small value(More)