Synthesis and effect of nonhydrolyzable xanthosine triphosphate derivatives on prenylation of Rab5D136N
UMass Chan Affiliations
Department of Pharmacology and Molecular ToxicologyDocument Type
Journal ArticlePublication Date
1997-01-01Keywords
GTP PhosphohydrolasesGTP-Binding Proteins
Hydrolysis
Protein Prenylation
Ribonucleotides
rab5 GTP-Binding Proteins
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
A novel and convenient method for nucleoside triphosphate synthesis was applied to the preparation of potentially nonhydrolyzable xanthosine triphosphate derivatives. The N-methylimidazolide of xanthosine 5'-monophosphate reacted rapidly with methylenediphosphonic acid and imidodiphosphonic acid to give xanthosine 5'-(beta, gamma-methylene)triphosphate and xanthosine 5'-(beta, gamma-imido)triphosphate, respectively, in good yields. Both compounds inhibited the xanthosine-diphosphate-dependent prenylation of a mutant of Rab5, Rab5D136N, the nucleotide specificity of which had been converted from GTP to xanthosine triphosphate. The results indicate that xanthosine 5'-(beta, gamma-methylene)triphosphate and xanthosine 5'-(beta, gamma-imido)triphosphate bound to the mutant protein with similar affinities and were not hydrolyzed under the assay conditions. These novel derivatives may be useful tools for the study of the role of individual GTPases mutated to xanthosine triphosphate specificity in the background of other GTP-binding proteins.Source
Mol Pharmacol. 1997 Jan;51(1):47-51.
DOI
10.1124/mol.51.1.47Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38611PubMed ID
9016345Related Resources
ae974a485f413a2113503eed53cd6c53
10.1124/mol.51.1.47