Interaction of GTP derivatives with cellular and oncogenic ras-p21 proteins.
A series of N2-substituted guanosine 5'-triphosphates was synthesized from the corresponding nucleosides. The nucleosides were prepared by treatment of N2-substituted guanines with tetra-O-acetylribose under conditions which maximized the yield of the 9-beta-guanosine isomers. These nucleotides and several sugar- and base-modified analogues of GTP were tested for their ability to bind to cellular and oncogenic forms of the GTP/GDP binding proteins, Ha-ras-p21. Several N2-substituted GTPs showed affinities higher than that of GDP itself, and the N2-[p-(n-butyl)phenyl] derivative bound to the oncogenic mutant, Leu-61 p21, twice as strongly as to the cellular protein. Changes in relative affinities of the nucleotides are discussed with reference to reported crystallographic structures of p21.
Noonan
T
T
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Brown
N
N
Dudycz
L
L
Wright
G
G
D011905:Genes, ras; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D015394:Molecular Structure; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D011993:Recombinant Fusion Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)