Controlled synthesis of O-glycopolypeptide polymers and their molecular recognition by lectins

TY - JOUR

T1 - Controlled synthesis of O-glycopolypeptide polymers and their molecular recognition by lectins

AU - Pati, Debasis

AU - Shaikh, Ashif Y.

AU - Das, Soumen

AU - Nareddy, Pavan Kumar

AU - Swamy, Musti J.

AU - Hotha, Srinivas

AU - Gupta, Sayam Sen

PY - 2012/5/14

Y1 - 2012/5/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84861175987&partnerID=8YFLogxK

U2 - 10.1021/bm201813s

DO - 10.1021/bm201813s

M3 - Journal article

C2 - 22497456

AN - SCOPUS:84861175987

SN - 1525-7797

VL - 13

SP - 1287

EP - 1295

JO - Biomacromolecules

JF - Biomacromolecules

IS - 5

ER -