Design control compounds

Knowledge of the intracellular thermodynamics and kinetics of metal metabolism may become useful in the design of compounds that alter intracellular metal ion availability. This in turn may be useful in controlling such biological phenomena as cancer cell proliferation, disorders of metal metabolism, and metal-induced neurotoxicity. 

Hydrazide 1 was designed as the CA anchor fragment and hence necessitated dual functionality an Ar-SO NH moiety for reliable CA affinity and a hydrazide moiety to take part in hydrazone exchange. Hydrazide 2 lacked the sulfonamide moiety of 1, but was still able to participate in hydrazone exchange and thus functioned as a control compound. Fragments A-E, the exchange partners for 1 and 2, were selected to introduce an array of tails onto 1 to enable exploration of periphery recognition interactions with CA. 

Thus we designed and synthesized a bicyclic pyridoxamine derivative carrying an oriented catalytic side arm (16) [11], Rates for conversion of the ketimine Schiff base into the aldimine, formed with 26 (below) and a-ketovaleric acid, indolepyruvic acid, or pyruvic acid, were enhanced 20-30 times relative to those carried out in the presence of the corresponding pyridoxamine derivatives without the catalytic side arm. With a-ketovaleric acid, 16 underwent transamination to afford D-norvaline with 90% ee. The formation of tryptophan and alanine from indolepyruvic acid and pyruvic acid, respectively, showed a similar preference. A control compound (17), with a propylthio group at the same stereochemical position as the aminothiol side arm in 16, produced a 1.5 1 excess of L-norvaline, in contrast to the large preference for D-amino acids with 16. Therefore, extremely preferential protonation seems to take place on the si face when the catalytic side arm is present as in 16. 

Under Subtitle C of the Resource Conservation and Recovery Act (RCRA), certain wastes containing designated TPH compounds and petroleum-related industrial wastes are listed as hazardous. However, RCRA excludes some TPH-related wastes from regulations (e.g., certain exploration, well development, and productions wastes). The RCRA-listed wastes are also controlled under the Comprehensive Environmental, Response, Compensation, and Liability Act (CERCLA) for accidental releases to the environment. 

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