Synthesis of a Bisubstrate-Type Inhibitor of N-Acetylglucosaminyltransferases†
Shinya Hanashima Dr.
RIKEN (The Institute of Physical and Chemical Research), 2–1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, Fax: (+81) 48-462-4680
Search for more papers by this authorShino Manabe Dr.
RIKEN and PRESTO, Japan Science and Technology Agency (JST), Japan
Search for more papers by this authorKei-ichiro Inamori Dr.
Department of Biochemistry, Osaka University Medical School, 2–2 Yamadaoka, Suita, Osaka 565-0871, Japan
Search for more papers by this authorNaoyuki Taniguchi Prof. Dr.
Department of Biochemistry, Osaka University Medical School, 2–2 Yamadaoka, Suita, Osaka 565-0871, Japan
Search for more papers by this authorYukishige Ito Dr.
RIKEN (The Institute of Physical and Chemical Research), 2–1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, Fax: (+81) 48-462-4680
Search for more papers by this authorShinya Hanashima Dr.
RIKEN (The Institute of Physical and Chemical Research), 2–1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, Fax: (+81) 48-462-4680
Search for more papers by this authorShino Manabe Dr.
RIKEN and PRESTO, Japan Science and Technology Agency (JST), Japan
Search for more papers by this authorKei-ichiro Inamori Dr.
Department of Biochemistry, Osaka University Medical School, 2–2 Yamadaoka, Suita, Osaka 565-0871, Japan
Search for more papers by this authorNaoyuki Taniguchi Prof. Dr.
Department of Biochemistry, Osaka University Medical School, 2–2 Yamadaoka, Suita, Osaka 565-0871, Japan
Search for more papers by this authorYukishige Ito Dr.
RIKEN (The Institute of Physical and Chemical Research), 2–1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, Fax: (+81) 48-462-4680
Search for more papers by this authorS.H. is a recipient of the Special Postdoctoral Researcher Program Fellowship in RIKEN. Additional financial support from CREST (JST) is acknowledged. We thank Dr. T. Chihara and his staff for elemental analyses and Dr. H. Koshino and Ms. T. Chijimatsu for NMR measurements. We thank Ms. Akemi Takahashi for her technical assistance.
Graphical Abstract
Transfer interference: Synthesis of the bisubstrate-type N-acetylglucosaminyltransferase (GnT) inhibitor 1 was achieved by a polymer-resin hybrid capture–release strategy for the construction of the acceptor component. One-pot ligation in aqueous media produced the coupling product, and subsequent construction of a diphosphate linkage led to 1. Inhibitory activities toward GnT-V and GnT-IX were evaluated and revealed the potency of 1 toward the latter enzyme.
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