Enhanced activity or resistance of adenosine derivatives towards adenosine deaminase-catalyzed deamination: Influence of ribose modifications

Giulio Vistoli, Alessandro Pedretti, Laura Alessandrini, Silvana Casati, Pierangela Ciuffreda, Giuseppe Meroni, Enzo Santaniello

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2877-2879
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number10
DOIs
Publication statusPublished - May 15 2009

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Keywords

  • Adenosine analogues
  • Adenosine deaminase
  • Adenosine derivatives
  • Molecular docking

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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