TY - JOUR
T1 - Bioconjugation with Thiols by Benzylic Substitution
AU - Watanabe, Kenji
AU - Ohshima, Takashi
N1 - Funding Information:
Grant-in-Aid for Scientific Research on Innovative Areas (JSPS KAKENHI Grant Number JP15H05846 in Middle Molecular Strategy for T.O.) and Grant-in-Aid for Young Scientists (B) (JSPS KA-KENHI Grant Number 16K17902 for K.W.) from JSPS, Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED (for T.O. and K.W.). K.W. acknowledges Ajinomoto Award in Synthetic Organic Chemistry, Japan for financial support. The authors acknowledge Drs. Hiroyuki Morimoto and Kazutru Usui for discussion in the reaction mechanism and CD measurement. The authors acknowledge Ms. Megumi Noshita, Mr. Ryohei Yonesaki and Mr. Tsukushi Tanaka for help in HRMS measurement.
Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/3/15
Y1 - 2018/3/15
N2 - A benzylic substitution of 3-indolyl(hydroxyl)acetate derivatives with thiols proceeded specifically in the presence of amino, carboxy, and phosphate groups in weakly acidic aqueous solutions under nearly physiological condition, while no reaction occurred at pH over 7. Kinetic studies revealed that the reaction followed second-order kinetics (first-order in the reactant and first-order in thiol) in contrast with the SN1 mechanism of common benzylic substitution of alcohols. The utility of the present method for functionalization of biomacromolecules was demonstrated using several model proteins, such as lysozyme, insulin, trypsin, and serum albumin. The catalytic bioactivity of lysozyme in lysis of Micrococcus lysodeikticus cells was completely retained after the modification.
AB - A benzylic substitution of 3-indolyl(hydroxyl)acetate derivatives with thiols proceeded specifically in the presence of amino, carboxy, and phosphate groups in weakly acidic aqueous solutions under nearly physiological condition, while no reaction occurred at pH over 7. Kinetic studies revealed that the reaction followed second-order kinetics (first-order in the reactant and first-order in thiol) in contrast with the SN1 mechanism of common benzylic substitution of alcohols. The utility of the present method for functionalization of biomacromolecules was demonstrated using several model proteins, such as lysozyme, insulin, trypsin, and serum albumin. The catalytic bioactivity of lysozyme in lysis of Micrococcus lysodeikticus cells was completely retained after the modification.
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U2 - 10.1002/chem.201706149
DO - 10.1002/chem.201706149
M3 - Article
C2 - 29457301
AN - SCOPUS:85042086068
VL - 24
SP - 3959
EP - 3964
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 16
ER -