Combining glycocluster synthesis with protein engineering: an approach to probe into the significance of linker length in a tandem-repeat-type lectin (galectin-4).
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.
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany.
Sabine
S
André
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland.
Guan-Nan
GN
Wang
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany.
Hans-Joachim
HJ
Gabius
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland. Electronic address: paul.v.murphy@nuigalway.ie.
Paul V
PV
Murphy
D000595:Amino Acid Sequence; D060326:Chemistry Techniques, Synthetic; D003094:Collagen / Q000737:chemistry; D037541:Galectin 4 / Q000737:chemistry*; D006023:Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015202:Protein Engineering; D020449:Repetitive Sequences, Amino Acid
D037541:Galectin 4; D006023:Glycoproteins; D003094:Collagen
Agglutinin; Glycoprotein; Lectin; Modelling; Terephthalamides; Triazoles