Enhanced activity or resistance of adenosine derivatives towards adenosine deaminase-catalyzed deamination: Influence of ribose modifications.
The effect of the presence of the 1'-C-methyl group and 2',3'-O-substitution in the adenosine structure on ADA activity has been investigated by modeling studies. Results show that the 2'- and 3'-O- substituents are harbored in a quite large cavity of intermediate polarity, whereas the 1'-C-substituent clashes against Ala180 distorting the architecture of the catalytic centre. Globally, the study emphasizes the ability of ADA to transform a large set of 2',3'-O-substituted adenosine analogues as well as the opportunity to design 1'-C-substituted adenosine derivatives resistant to ADA-catalyzed deamination.
Vistoli
Giulio
G
Dipartimento di Scienze Farmaceutiche 'Pietro Pratesi', Università degli Studi di Milano, Milan, Italy.
Pedretti
Alessandro
A
Alessandrini
Laura
L
Casati
Silvana
S
Ciuffreda
Pierangela
P
Meroni
Giuseppe
G
Santaniello
Enzo
E
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000243:Adenosine Deaminase / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D003198:Computer Simulation; D003641:Deamination; D012266:Ribose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D012266:Ribose; D000243:Adenosine Deaminase; D000241:Adenosine