Back to Search
Start Over
Synthesis and Evaluation of Alternative Substrates for Arginasease
- Source :
-
Bioorganic Chemistry . Apr2002, Vol. 30 Issue 2, p81. 14p. - Publication Year :
- 2002
-
Abstract
- Two novel carboxyl-containing arginase substrates, 4-guanidino-3-nitrobenzoic acid and 4-guanidino-2-nitrophenylacetic acid, have been synthesized and found to give enhanced catalysis and dramatically lower Km values relative to 1-nitro-3-guanidinobenzene, a substrate designed for use in a chromophoric arginase assay. To more efficiently mimic the natural substrate, a series of sulfur analogs of l-arginine were synthesized and kinetically characterized. The parent compound, l-thioarginine, with the bridging guanidinium nitrogen of l-arginine replaced with sulfur, functions as efficiently as the natural substrate. The desamino analog shows extremely low turnover, while the kcat of the descarboxy analog is only 75-fold lower than that of arginine. These results suggest that the bridging nitrogen of l-arginine is not important for either substrate binding or catalysis, while the α-carboxyl group facilitates substrate binding, and the α-amino group is necessary for efficient catalysis. Isothiourea homologs previously reported to be nitric oxide synthase inhibitors have been found to undergo a rapid non-enzymatic rearrangement to a species that is probably the true inhibitor. [Copyright &y& Elsevier]
- Subjects :
- *ARGININE
*SULFUR compounds
Subjects
Details
- Language :
- English
- ISSN :
- 00452068
- Volume :
- 30
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Bioorganic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 8500737
- Full Text :
- https://doi.org/10.1006/bioo.2001.1228