The enzyme sirtuin 1 (SIRT1) is a major target for the treatment of various metabolic disorders. Herein, a practical synthesis of imidazo[1,2-b]thiazole derivatives, one of the most comprehensively studied class of synthetic SIRT1 activators, is presented. The synthesized SIRT1 activators, the in vitro-identified metabolite of SRT1720, and the eightfold deuterated analytical standards were obta...

The effects of purified soluble fibrin and of fibrinogen fragments (fibrin mimic) on the activation of Lysplasminogen (i.e. plasminogen residues 77-790) to plasmin by streptokinase plasminogen activator complex and by tissue-type plasminogen activator were studied. Dissociation constants of both activators were estimated to lie in the range 90-160 nm (fibrin) and 16-60 nM (CNBr-cleavage fragmen...

Phosphoenolpyruvate carboxylase from Salmonella typhimurium is shown to consist of four subunits of molecular weight about 100,000. Guanidinium chloride and 0.1% sodium dodecyl sulfate only partially dissociate the carboxymethylated subunits into monomers of molecular weight of about 50,000. Only one NH*-terminal residue, methionine, is found by the dansylation procedure, which together with pe...

Cultured thioglycollate-stimulated peritoneal macrophages synthesize, accumulate, and continuously release high levels of plasminogen activators for at least 4 days whereas cultures of unstimulated macrophages do not; the higher specific catalytic activity of released vs. cell-associated enzyme suggests that the plasminogen activators are actively secreted. The major macrophage plasminogen acti...

Adenylyl cyclase activity can be reconstituted by simple mixture of the two cytosolic domains of the enzyme after their independent synthesis in Escherichia coli. We have synthesized and purified the C1a domain of type I adenylyl cyclase and the C2 domain of the type II enzyme to assess their interactions with each other and with the activators Gsalpha and forskolin. In the absence of an activa...

It is recognized that high-throughput enzyme inhibition screens often return nonspecific inhibitors as "hits". Recently, high-throughput screens for enzyme activators have led to the identification of several compounds with novel and potent biological activity. Here, we show that enzyme activation screens can also uncover compounds that activate multiple enzymes in a nonspecific fashion. Descri...

Riboswitches are conserved regions within mRNA molecules that bind specific metabolites and regulate gene expression. TPP-riboswitches, which respond to thiamine pyrophosphate (TPP), are involved in the regulation of thiamine metabolism in numerous bacteria. As these regulatory RNAs are often modulating essential biosynthesis pathways they have become increasingly interesting as promising antib...

The cover shows an artistic concept describing evolutional approach to the generation of dynamic inhibitors and activators Carbonic Anhydrase on both molecular supramolecular levels through implementation reversible covalent reactions non-covalent intermolecular interactions within inner active catalytic center outer enzyme microenvironment, respectively. They open up wide perspectives construc...