Characterisation of glycoprotein ligands synthesised using solid-phase combinatorial chemistry.
A combination of rational design based on mimicking natural protein-carbohydrate interactions and solid-phase combinatorial chemistry has led to the identification of an affinity ligand which displays selectivity for the mannose moiety of glycoproteins. The ligand was initially identified as 32/18, a triazine scaffold substituted with 2-acetylpyrrole (32) and 5-aminoindan (18). However, characterisation of the immobilised ligand by release from the matrix via a cleavable linker, (4s,5s)-4,5-di(aminomethyl)-2,2-dimethyldioxolane, and using a non-destructive on-resin method, 13C NMR spectroscopy, confirmed that the putative ligand 32/18 was, in fact, 18/18, the disubstituted 5-aminoindan. 1H NMR studies on the interaction of alpha-D-methylmannoside with the ligand 18/18 in solution confirm the involvement of the hydroxyl group in the C-2 position.
Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 IQT, UK. umadevi@sirim.my
Uma D
UD
Palanisamy
Christopher R
CR
Lowe
D020650:Combinatorial Chemistry Techniques; D006023:Glycoproteins / Q000378:metabolism*; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D013056:Spectrophotometry, Ultraviolet
D006023:Glycoproteins; D008024:Ligands