NMR-based exploration of the acceptor binding site of human blood group B galactosyltransferase with molecular fragments

Christoph Rademacher, Jens Landström, Nora Sindhuwinata, Monica M. Palcic, Göran Widmalm, Thomas Peters*

*Corresponding author for this work
20 Citations (Scopus)


A substantial body of work has been devoted to the design and synthesis of glycosyltransferase inhibitors. A major obstacle has always been the demanding chemistry. Therefore, only few potent and selective inhibitors are known to date. Glycosyltransferases possess two distinct binding sites, one for the donor substrate, and one for the acceptor substrate. In many cases binding to the donor site is well defined but data for acceptor binding is sparse. In particular, acceptor binding sites are often shallow, and in many cases the dimensions of the binding pocket are not well defined. One approach to glycosyltransferase inhibitors is to chemically link donor site and acceptor site ligands to generate high affinity binders. Here, we describe a novel approach to identify acceptor site ligands from a fragment library. We have chosen human blood group B galactosyltransferase (GTB) as a biologically important model target. The approach utilizes a combination of STD NMR, spin-lock filtered NMR experiments and surface plasmon resonance measurements. Following this route we have identified molecular fragments from a fragment library that bind to the acceptor site of GTB with affinities of the order of a natural acceptor substrate. Unlike natural substrates these fragments allow for straightforward chemical modifications and, therefore will serve as scaffolds for potent GTB inhibitors. In general, the approach described is applicable to any glycosyltransferase and may assist in the development of novel glycosyltransferase inhibitors.

Original languageEnglish
JournalGlycoconjugate Journal
Issue number3
Pages (from-to)349-358
Number of pages10
Publication statusPublished - 04.2010

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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