TY - JOUR
AU - Diederich, François
AB - A lipophilic pocket at the tRNA‐guanine transglycosylase (TGT) enzyme active site was discovered and a substantial contribution to the substrate binding free energy was observed when this pocket was filled by apolar side chains. A family of new inhibitors of TGT was developed by employing the principles of molecular recognition and structure‐based de novo design, and shown to display up to submicromolar binding affinity. Two X‐ray structures of TGT–inhibitor complexes confirmed the binding mode predicted in the design stage. An exceptional ”point mutation” effect on binding affinity was observed upon substitution of X=CH2 in 1 with O or S.
TI - De Novo Design, Synthesis, and In Vitro Evaluation of Inhibitors for Prokaryotic tRNA‐Guanine Transglycosylase: A Dramatic Sulfur Effect on Binding Affinity
JO - ChemBioChem
DO - 10.1002/1439-7633(20020301)3:2/3<250::AID-CBIC250>3.0.CO;2-J
DA - 2002-01-01
UR - https://www.deepdyve.com/lp/wiley/de-novo-design-synthesis-and-in-vitro-evaluation-of-inhibitors-for-VuizvhiVSD
SP - 250
EP - 253
VL - 3
IS - 2‐3
DP - DeepDyve
ER -