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Carbohydr Res. 2014 May 7;389:25-38. doi: 10.1016/j.carres.2013.12.024. Epub 2014 Jan 11.

Combining glycocluster synthesis with protein engineering: an approach to probe into the significance of linker length in a tandem-repeat-type lectin (galectin-4).

Author information

1
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany.
2
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland.
3
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland. Electronic address: paul.v.murphy@nuigalway.ie.

Abstract

Complementarity in lectin-glycan interactions in situ is assumed to involve spatial features in both the lectin and the glycan, giving a functional meaning to structural aspects of the lectin beyond its carbohydrate-binding site. In combining protein engineering with glycocluster synthesis, it is shown that the natural linker length of a tandem-repeat-type human lectin (galectin-4) determines binding properties in two binding assays (using surface-presented glycoprotein and cell surface assays). The types of glycocluster tested included bivalent lactosides based on tertiary amides of terephthalic, isophthalic, 2,6-naphthalic and oxalic acids as well as bivalent H(type 2) trisaccharides grafted on secondary/tertiary terephthalamides and two triazole-linker-containing cores. The presented data reveal a marked change in susceptibility to the test compounds when turning the tandem-repeat-type to a proto-type-like display. The testing of glycoclusters is suggested as a general strategy to help to delineate the significance of distinct structural features of lectins beyond their contact sites to the glycan.

KEYWORDS:

Agglutinin; Glycoprotein; Lectin; Modelling; Terephthalamides; Triazoles

PMID:
24698724
DOI:
10.1016/j.carres.2013.12.024
[Indexed for MEDLINE]

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