Cell-Effective Transition-State Analogue of Phenylethanolamine -Methyltransferase.

Phenylethanolamine -methyltransferase (PNMT) catalyzes the -adenosyl-l-methionine (SAM)-dependent methylation of norepinephrine to form epinephrine. Epinephrine is implicated in the regulation of blood pressure, respiration, Alzheimer's disease, and post-traumatic stress disorder (PTSD). Transition-state (TS) analogues bind their target enzymes orders of magnitude more tightly than their substrates.

Aldehyde-Based Inhibitors of the Peptidoglycan O-Acetylesterase Ape.

The O-acetylation of the muramic acid residues in peptidoglycan (PG) is a modification that protects the bacteria from lysis due to the action of lysozyme. In Gram-negative bacteria, deacetylation is required to allow lytic transglycosylases to promote PG cleavage during cell growth and division. This deacetylation is catalyzed by O-acetylpeptidoglycan esterase (Ape) which is a serine esterase and employs covalent catalysis via a serine-linked acyl enzyme intermediate.

A guanidinium-based inhibitor of a type I isopentenyl diphosphate isomerase.

An inhibitor bearing a phosphinylphosphonate group appended to a guanidinium functionality was designed to inhibit enzymes that generate carbocations from dimethylallyl diphosphate. When tested against human farnesyl diphosphate synthase the inhibitor bound with high micromolar affinity and did not bind more tightly than an isosteric inhibitor lacking the guanidinium functionality. When tested against the Type I isopentenyl diphosphate:dimethylallyl diphosphate isomerase from Escherichia coli, the inhibitor bound with a K value of 120 nM, which was 400 times greater than its isosteric counterpart.

Transition-State Analogues of Phenylethanolamine -Methyltransferase.

Phenylethanolamine -methyltransferase (PNMT) is a critical enzyme in catecholamine synthesis. It transfers the methyl group of -adenosylmethionine (SAM) to catalyze the synthesis of epinephrine from norepinephrine. Epinephrine has been associated with diverse human processes, including the regulation of blood pressure and respiration, as well as neurodegeneration found in Alzheimer's disease.

Potential rearrangements in the reaction catalyzed by the indole prenyltransferase FtmPT1.

The indole prenyltransferase FtmPT1 catalyzes the C-2 normal prenylation of brevianamide F (cyclo-L-Trp-L-Pro) to give tryprostatin B. A previous structural analysis and studies with alternate substrates suggest that the reaction might not proceed through a direct C-2 attack, but could involve a C-3 prenylation followed by a rearrangement. In this work we investigated the reactivity of FtmPT1 with tryptophan, 5-hydroxybrevianamide, and 2-methylbrevianamide, and isolated products that had been reverse prenylated at C-3 and normal prenylated at N-1, C-3, or C-4.

3-(1-Adamantylamino)-3-methyl-1-phenyl-quinoline-2,4(1H,3H)-dione.

The structure of the title compound, C(26)H(28)N(2)O(2), contains essentially planar quinoline and benzene rings, the maximum deviations from the best plane being 0.086 (2) and 0.0056 (19) Å, respectively; the dihedral angle between the rings is 82.