Adenosine triphosphate -competitive

In the processes that require regeneration of cofactors such as nicotinamide adenine dinucleotide phosphate (NAD(P)H) and adenosine triphosphate (ATP), whole-cell biotransformations are more advantageous than enzymatic systems [12,15]. Whole cells also have a competitive edge over the isolated enzymes in complex conversions involving multiple enzymatic reactions [14]. 

Since active transport often requires energy in the form of adenosine triphosphate (ATP), compounds or conditions that inhibit energy production (e.g., iodoac-etate, fluoride, cyanide, anaerobiosis) will impair active transport. The transport of a given compound also can be inhibited competitively by the coadministration of other compounds of sufficient structural similarity that they can compete with the first substance for sites on the carrier protein. 

Ruboxistaurin (LY333531) 41 (Eli Lilly) is being evaluated in a Phase III trial for the treatment of diabetic macular oedema.224 Lilly had submitted an NDA in February 2006 to the FDA for the treatment of diabetic retinopathy and received an Approvable Letter in September 2006 that requested another Phase III trial for additional efficacy data. The EMEA also required further clinical data and, as a consequence, Lilly withdrew its European MAA. Ruboxistaurin 41225 228 competitively inhibits adenosine triphosphate (ATP) binding to PKC/i and is a synthetic analogue of staurosporine 42. 

The conformations of nucleotides have been probed by lanthanides [73]. Furthermore, adenosine triphosphate (ATP)-lanthanide complexes are strong enough to carry the metal on to enzymes. Thus, Gd " competitively inhibits Mg -(yeast)-phosphoglycerate kinase (mol. wt. 47000) and selectively broadens histidine H resonances [74]. 

Probably all adenylyl cyclases are inhibited competitively by substrate analogs, which bind at the site and to the enzyme configuration with which cation-ATP binds (cf Fig. 4). One of the best competitive inhibitors is (3-L-2, 3 -dideoxy adenosine-5 -triphosphate ( 3-L-2, 3 -dd-5 -ATP Table 4) [4], which allowed the identification of the two metal sites within the catalytic active site (cf Fig. 4) [3]. This ligand has also been labeled with 32P in the (3-phosphate and is a useful ligand for reversible, binding displacement assays of adenylyl cyclases [4]. The two inhibitors, 2, 5 -dd-3 -ATP and 3-L-2, 3 -dd-5 -ATP, are comparably potent... 

Finally, a lead optimization program that utilized a strategy to maximize LipE in a series of aminopyrrolidines produced the broadly selective, potent adenosine-5 -triphosphate (ATP)-competitive Akt inhibitor 11 (Akt IC50 < 1 nM, clogP = 2.4, LipE = 7.2) which was nominated for clinical development [18]. 

Murray and Friedrichs (80) have obtained a 5 -nucleotidase from a particulate fraction of Ehrlich ascites tumor cells using deoxycholate. The relative rates of hydrolysis of 5 -UMP, 5 -AMP, 5 -CMP, 5 -GMP, and 5 -IMP are 129, 100, 93, 83, and 79, respectively. Adenosine and thymidine triphosphate are competitive inhibitors of 5 -AMP hydrolysis... 

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