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CAL‐B‐Catalyzed Acylation of Nucleosides and Role of the Sugar Conformation: An Improved Understanding of the Enzyme‐Substrate Recognition
Author(s) -
MartínezMontero Saúl,
Fernández Susana,
Sanghvi Yogesh S.,
Gotor Vicente,
Ferrero Miguel
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200609
Subject(s) - chemistry , acylation , candida antarctica , ring (chemistry) , stereochemistry , substrate (aquarium) , nucleoside , sugar , enzyme , nuclear magnetic resonance spectroscopy , catalysis , lipase , biochemistry , organic chemistry , oceanography , geology
We demonstrate that the sugar ring conformation of nucleosides plays a critical role during Candida antarctica lipase B (CAL‐B) catalyzed acylation. Specifically, the North ( N ), but not the South ( S ) nucleoside sugar ring conformation is preferred for efficient binding at the catalytic site. In this study, we used nuclear magnetic resonance (NMR) spectroscopy experiments to establish the sugar ring conformation of nucleosides and performed molecular modeling studies to support the observations. The ribo‐ and 2′‐substituted (OMe, F) nucleosides displaying the N ‐conformation undergo rapid and facile acylation compared to the 2′‐deoxynucleosides with the S ‐conformation. This study improves our understanding of the critical role that sugar conformation plays in enzyme–substrate recognition during biotransformations using CAL‐B. To the best of our knowledge, this is the first experimental report offering a rationale for the observed selectivity during acylation of nucleosides containing the N ‐sugar conformation.