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)]
Références
- Titre
- Tetravalent glycocyclopeptide with nanomolar affinity to wheat germ agglutinin.
- Type de publication
- Article de revue
- Année de publication
- 2013
- Auteurs
- Fiore, Michele, Berthet Nathalie, Marra Alberto, Gillon Emilie, Dumy Pascal, Dondoni Alessandro, Imberty Anne, and Renaudet Olivier
- Revue
- Org. Biomol. Chem.
- Volume
- 11
- Pagination
- 7113–7122
- ISSN
- 1477-0520
- Mots-clés
- Click chem copper catalyst oxime ligation thyol ene coupling cyclic peptide solid phase synthesis alkyne azide cycloaddn copper glycocluster isothermal titrn calorimetry assocn const WGA complexation glycocyclopeptide synthesis glycocluster wheat germ agglutinin inhibitor adhesion thiol ene coupling r
Soumis le 12 avril 2018