Methionine sulfoxide reductase A (MsrA) catalyzes the reduction of methionine sulfoxide to methionine and is specific for the S epimer of methionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing methionine sulfoxide residues in proteins back to methionine. Because oxidation of methionine residues is reversible, this covalent modification could also functio...

The stereospecific ring-opening of O-heterocycles to provide acyclic alcohols and carboxylic acids with controlled formation of a new C-C bond is reported. These reactions provide new methods for synthesis of acyclic polyketide analogs with complex stereochemical arrays. Stereoselective synthesis of the cyclic template is utilized to control relative configuration; subsequent stereospecific nic...

The molecular nature and configuration of the opiate receptor is a problem under intensive investigation in a number of laboratories (1,2,3). Our interest in the problem developed as a result of a finding of others (4) that a proteolipid fraction from brain may be responsible for stereospecific opiate binding observed in various preparations of brain tissue. Upon examining various lipids, prote...

Using a water-based prebiotic model of sugar synthesis involving glycolaldehyde self-condensation, we demonstrate that homochiral L-dipeptide catalysts lead to the stereospecific syntheses of tetroses. The asymmetric effect is largest for erythrose, which may reach a D-enantiomeric excess of >80% with L-Val-L-Val catalyst. Based on results obtained with various peptides, we propose a possible c...

Protease inhibitors are key components in the chemotherapy of HIV infection. However, the appearance of viral mutants routinely compromises their clinical efficacy, creating a constant need for new and more potent inhibitors. Recently, a new class of epoxide-based inhibitors of HIV-1 protease was investigated and the configuration of the epoxide carbons was demonstrated to play a crucial role i...

Inhibitors of human lactate dehydrogenase A (LDH-A) are promising therapeutic agents against cancer. The development of LDH-A inhibitors that possess cellular activities has so far proved to be particularly challenging, since the enzyme's active site is narrow and highly polar. In the recent past, we were able to develop a glucose-conjugated N-hydroxyindole-based LDH-A inhibitor designed to exp...

Pyruvate formate-lyase activating enzyme generates a stable and catalytically essential glycyl radical on G(734) of pyruvate formate-lyase via the direct, stereospecific abstraction of a hydrogen atom from pyruvate formate-lyase. The activase performs this remarkable feat by using an iron-sulfur cluster and S-adenosylmethionine (AdoMet), thus placing it among the AdoMet radical superfamily of e...

Olefin polymerization catalysis is a domain of major research activity. For the last decade, much of this research has been focused in the area of metallocene catalysis, which has been at the front line in driving important technology renewal in the polyolefins industry. Developments in metallocene catalysis have instigated much trade press discussion, and now emerging nonmetallocene catalyst s...

o-Quinodimethanes have remarkable utility as reactive intermediates in Diels–Alder reactions, enabling significantly accelerated routes to complex polycyclic compounds. The discovery of different discrete precursors thermally generate o-quinodimethanes thereby greatly augmented their availability and versatility. However, due the required high temperatures immense reactivity o-quinodimethanes, ...