earticle

영어

Glycosylation, the attachment of sugars to proteins, is one of the most abundant post translational modifications in all living cells. It plays very important roles in protein folding, stabilization, embryogenesis, neuronal development, cell-cell adhesion and recognition. Glycosylation produces huge structural diversity in proteins which is necessary for the functionalization of nascent proteins. While peptides are an attractive class of molecules to synthesize glycopeptides, they possess undesirable drawbacks including sensitivity to proteases, limited cell permeability and poor bioavailability. Thus, there have been increasing needs for new peptidomimetics with improved pharmacokinetic characteristics. Among them, peptoids, N-alkylated glycine oligomers where side chains are directly attached to nitrogen atom rather than α-carbon of peptide, possess many advantages over peptides. Attachments of sugars to peptoid backbone generate glycopeptoids which have interesting features by mimicking glycopeptides. Our strategy was to install sugar derivatives to alkenyl moiety-containing peptoids through solid-phase cross metathesis approach. The peptoids were prepared on bead having strategically positioned alkenyl moieties in different length. O-linked sugar-alkene derivatives based upon glucose, mannose, and galactose monomers were also made. Initially, we screened reaction condition parameters such as catalyst, concentration of sugar derivative, temperature, solvent, and reaction time. HG2 was proved to be a better catalyst than G1 and G2. The length of alkenyl moieties was critical on cross metathesis. The cross metathesis was facilitated easily with 3-butenyl group over allyl group. We have successfully synthesized glycopeptoids on solid-phase through cross metathesis in very good yields. This systematic study into the use of solid-phase cross metathesis for the synthesis of glycopeptoids provides a particularly valuable tool for easy access to the molecular sources of glycopeptidomimetics and the rapid generation of glycopeptoid libraries.