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 language | English |
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Pages (from-to) | 2877-2879 |
Number of pages | 3 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 19 |
Issue number | 10 |
DOIs | |
Publication status | Published - May 15 2009 |
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