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Synthesis, Evaluation, and Mechanism of N , N , N ‐Trimethyl‐ D ‐glucosamine‐(1→4)‐chitooligosaccharides as Selective Inhibitors of Glycosyl Hydrolase Family 20 β‐ N ‐Acetyl‐ D ‐hexosaminidases
Author(s) -
Yang You,
Liu Tian,
Yang Yongliang,
Wu Qingyue,
Yang Qing,
Yu Biao
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000561
Subject(s) - chemistry , glycoside hydrolase , stereochemistry , glycosyl , enzyme , glucosamine , active site , hydrolase , docking (animal) , biochemistry , bioorganic chemistry , medicine , nursing
GH20 β‐ N ‐acetyl‐ D ‐hexosaminidases are enzymes involved in many vital processes. Inhibitors that specifically target GH20 enzymes in pests are of agricultural and economic importance. Structural comparison has revealed that the bacterial chitindegrading β‐ N ‐acetyl‐ D ‐hexosaminidases each have an extra +1 subsite in the active site; this structural difference could be exploited for the development of selective inhibitors. N , N , N trimethyl‐ D ‐glucosamine (TMG)‐chitotriomycin, which contains three GlcNAc residues, is a natural selective inhibitor against bacterial and insect β‐ N ‐acetyl‐ D ‐hexosaminidases. However, our structural alignment analysis indicated that the two GlcNAc residues at the reducing end might be unnecessary. To prove this hypothesis, we designed and synthesized a series of TMG‐chitotriomycin analogues containing one to four GlcNAc units. Inhibitory kinetics and molecular docking showed that TMG‐(GlcNAc) 2 , is as active as TMG‐chitotriomycin [TMG‐(GlcNAc) 3 ]. The selective inhibition mechanism of TMG‐chitotriomycin was also explained.