Controlled Synthesis of O-Glycopolypeptide Polymers and Their Molecular Recognition by Lectins

Abstract

The facile synthesis of high molecular weight water-soluble O-glycopolypeptide polymers by the ring-opening polymerization of their corresponding N-carboxyanhydride (NCA) in very high yield (overall yield > 70%) is reported. The per-acetylated-O-glycosylated lysine-NCA monomers, synthesized using stable glycosyl donors and a commercially available protected amino acid in very high yield, was polymerized using commercially available amine initiators. The synthesized water-soluble glycopolypeptides were found to be α-helical in aqueous solution. However, we were able to control the secondary conformation of the glycopolypeptides (α-helix vs nonhelical structures) by polymerizing racemic amino acid glyco NCAs. We have also investigated the binding of the glycopolypeptide poly(α-manno-O-lys) with the lectin Con-A using precipitation and hemagglutination assays as well as by isothermal titration calorimetry (ITC). The ITC results clearly show that the binding process is enthalpy driven for both α-helical and nonhelical structures, with negative entropic contribution. Binding stoichiometry for the glycopolypeptide poly(α-manno-O-lys) having a nonhelical structure was slightly higher as compared to the corresponding polypeptide which adopted an α-helical structure.

Stimuli‐responsive polypeptide materials prepared by ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides

“…65 They investigated the selective binding of the poly(a-manno-O-lys) with the lectin ConA using precipitation, hemagglutination assays, and isothermal titration calorimetry (ITC). 66 To investigate the secondary structure effects on the binding affinity, they also prepared racemic D,L-glycopolypeptides, and found that there is no significant difference in binding affinity between helical L-glycopolypeptide and racglycopolypeptide with random coil conformation. The ITC analysis also showed that the binding process is enthalpy driven for both a-helical and random coil structures.…”

Recent advances in glycopolypeptide synthesis

“…In a later report, Gupta and coworkers polymerized the same carbamate linked glycosylated lysine NCAs, as well as racemic and lactosylated versions, using acetate protecting groups instead of the previously reported benzoyl groups. 117 Polymerizations were again initiated with an amino terminal PEG in the presence of "proton sponge" in dioxane, but with acetate protecting groups these monomers gave molecular weights closer to theoretical values. Control over glycopolypeptide length was not demonstrated; however, narrow molecular weight distributions and degrees of polymerization from 35 to 64 were reported.…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

“…Changing the glycan moiety shown to change antibacterial activity (Talat et al, 2011) O-Glycosylated lysine-Ncarboxyanhydride monomers TOF (DHB) For synthesis of O-glycopolypeptide polymers (Pati et al, 2012b) Glycosylated MUC6 glycoprotein…”