| Summary: | 2-C-Substituted branched d-mannose analogues are novel monosaccharides, readily obtained from a Kiliani-acetonation sequence on d-fructose, followed by subsequent functional group manipulation. 2-C-Azidomethyl-d-mannose and 2-C-aminomethyl-d-mannose bind to the C-type lectin DC-SIGN (CD209) with significantly greater affinity than mannose. In particular, 2-C-aminomethyl-d-mannose exhibits a comparative 48-fold increase in binding as determined using a surface plasmon resonance-based competition assay. DC-SIGN is an important cell-surface type II transmembrane protein that interacts with blood group antigens, endogenous glycoproteins such as ICAM-3, and also deadly pathogens such as the human immunodeficiency and hepatitis C viruses. The effective use of small compounds to block target binding by mannose-selective C-type lectins at sub-millimolar concentrations has not been shown previously; thus, these data represent a very attractive thoroughfare to novel antiviral and immunomodulatory drug development. © 2007 Elsevier Ltd. All rights reserved.
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