Synthesis of Enzymatically Stable Analogues of GDP for Binding Studies with Transducin, the G-Protein of the Visual Photoreceptor.
The synthesis of five enzymatically stable analogues of guanosine diphosphate (GDP) has been carried out. The pyrophosphate moiety was mimicked in turn by the malonate, the acetophosphonate, the phosphonoacetate, the methylene-bis-phosphonate, and the imidodiphosphate groups. All the compounds were prepared via the synthesis of a transient fully protected nucleoside diphosphate analogue, and the final deprotection step was achieved by catalytic hydrogenolysis. The biological properties of the compounds have been evaluated toward transducin, the G-protein of the visual photoreceptor. Three guanosine imidodiphosphate derivatives bearing a linker at different positions on the sugar and on the base were then prepared and evaluated, giving some insight into the GDP binding site of transducin.
Vincent
Stéphane
S
Université Louis Pasteur de Strasbourg, Laboratoire de Synthèse Bioorganique associé au CNRS, Faculté de Pharmacie, 74, route du Rhin - BP 24 - 67 401 Illkirch Cedex, France, Université du Québec à Trois-Rivières, Département de chimie-biologie, Trois-Rivières (Québec) Canada, G9A 5H7, and CEA - CE Saclay, Service des Molécules Marquées, Bât. 547, Département de Biologie Moléculaire et Cellulaire, 91 191 Gif sur Yvette, France.
Grenier
Sonya
S
Valleix
Alain
A
Salesse
Christian
C
Lebeau
Luc
L
Mioskowski
Charles
C