Department of Chemistry Ugo Schiff, University of Florence , via della Lastruccia, 13-50019 Sesto F.no (FI) Italy.
ICBMS, University of Lyon , 43 Blvd. du 11 novembre 1918, 69622, Villeubanne Cedex, France.
Bioconjug Chem. 2018 Jan 17;29(1):83-88. doi: 10.1021/acs.bioconjchem.7b00616. Epub 2017 Dec 26.
Bacterial and fungal pathogens involved in lung infection in cystic fibrosis patients utilize a particular family of glycan-binding proteins, characterized by the presentation of six fucose-binding sites on a ring-shaped scaffold. These lectins are attractive targets for anti-infectious compounds that could interfere in the recognition of host tissues by pathogens. The design of a cyclopeptide-based hexavalent structure allowed for the presentation of six fucose residues. The synthetic hexavalent compound displays liable geometry resulting in high-avidity binding by lectins from Aspergillus fumigatus and Burkholderia ambifaria. Replacing the fucose residue with a conformationally constrained fucomimetic does not alter the affinity and provides fine specificity with no binding to other fucose-specific lectins.
参与囊性纤维化患者肺部感染的细菌和真菌病原体利用了一类特殊的聚糖结合蛋白，其特征在于环状支架上呈现六个岩藻糖结合位点。这些凝集素是抗传染性化合物的有吸引力的靶标，这些化合物可以干扰病原体对宿主组织的识别。基于环肽的六价结构的设计允许呈现六个岩藻糖残基。合成的六价化合物具有灵活的几何形状，导致烟曲霉和鲍曼不动杆菌的凝集素具有高亲和力结合。用构象受限的岩藻糖类似物替代岩藻糖残基不会改变亲和力，并提供精细的特异性，而与其他岩藻糖特异性凝集素无结合。
