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Enzymatic Glycosylation of Triazole‐Linked GlcNAc/Glc–Peptides: Synthesis, Stability and Anti‐HIV Activity of Triazole‐Linked HIV‐1 gp41 Glycopeptide C34 Analogues
Author(s) -
Huang Wei,
Groothuys Stan,
Heredia Alonso,
Kuijpers Brian H. M.,
Rutjes Floris P. J. T.,
van Delft Floris L.,
Wang LaiXi
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800741
Subject(s) - chemistry , glycopeptide , glycosylation , triazole , gp41 , oxazoline , stereochemistry , biochemistry , organic chemistry , biology , antigen , epitope , genetics , antibiotics , catalysis
Long‐lasting sweet proteins : The chemoenzymatic synthesis of a triazole (T)‐linked glycosylated C34 fragment from HIV‐1 gp41 is described. The glycopeptide shows high solubility, excellent fusion inhibition, and as shown in the graph, promising protease resistance.Endoglycosidase‐catalyzed transglycosylation of triazole‐linked glucose (Glc) and N ‐acetylglucosamine (GlcNAc)‐containing dipeptides and polypeptides was achieved by using synthetic sugar oxazoline as the donor substrate. It was found that both N‐ and C‐linked Glc/GlcNAc‐containing triazole derivatives were effective substrates for endo ‐β‐ N ‐acetylglucosaminidase from Arthrobacter (Endo‐A) for transglycosylation; this demonstrates a broad acceptor substrate specificity for Endo‐A. This chemoenzymatic method was successfully used for the synthesis of a novel triazole‐linked C34 glycopeptide derived from the HIV‐1 envelope glycoprotein, gp41. We found that the synthetic C34 glycopeptide possesses potent anti‐HIV activity with an IC 50 of 21 n M . The triazole‐linked C34 glycopeptide demonstrated a much enhanced stability against protease‐ and glycoamidase‐catalyzed digestion; this shows the protective effects of glycosylation and the stability of the triazole linkage. These favorable properties suggest that the triazole‐linked C34 glycopeptide might be valuable for further development as an anti‐HIV drug candidate.