Tetravalent glycocyclopeptide with nanomolar affinity to wheat germ agglutinin.

A series of tetravalent glycocyclopeptides functionalized with GlcNAc was synthesized using copper(I)-catalyzed alkyne-azide cycloaddn., oxime ligation and thiol-ene coupling. The binding ability of these compds. towards wheat germ agglutinin was studied by a competitive ELLA test and ITC expts. While all compds. were able to inhibit WGA binding to GlcNAc-polymer coated surfaces at low concns., deriv. 1 [H-Lys(GlcNAc)-Ala-Lys(GlcNAc)-Pro-Gly-Lys(GlcNAc)-Ala-Lys(GlcNAc)-Pro-Gly-OH] having an aliph. spacer and thioether linkage was 4.9 × 106 times more potent on a per sugar basis than GlcNAc. This remarkably strong effect was confirmed by ITC expts. as these revealed an assocn. const. of 9 nM for this compd., therefore presenting a gain of 200 000 times over GlcNAc. These results for compd. 1 represent the highest binding properties reported for WGA. [on SciFinder(R)]


Soumis le 12 avril 2018