Block-Sequence-Specific Glycopolypeptides with Selective Lectin Binding Properties.

Abstract

Glycopolypeptides with defined block sequences were prepared by sequential addition of two different N-carboxyanhydrides (NCAs), followed by selective deprotection and functionalization of predefined positions within the polypeptide backbone. The sequential arrangement of the galactose units and the block-sequence length have been systematically varied. All the glycopolypeptides have been obtained with a similar overall composition and comparable molecular weights. Circular dichroism measurements revealed some dependence of the secondary structure on the primary composition of the glycopolypeptides at physiological pH. While statistical, diblock, and tetrablock glycopolypeptides adopted a random coil conformation, the octablock glycopolypeptide was mostly α-helical. The ability to selectively bind to lectins was investigated by turbidity measurements as well as surface plasmon resonance (SPR) studies. It was found that the extent of binding was dependent on the position of the galactose units and thus the primary glycopolypeptide structure. The octablock glycopolypeptide favored interaction with lectin RCA120 while the tetrablock glycopolypeptide demonstrated the strongest binding activity to Galectin-3. The results suggest that different lectins are very sensitive to glyco coding and that precise control of carbohydrate units in synthetic polymeric glycopeptides will remain important.