RESUMO
1-(N-Phenyl)amino-1-deoxy-α-D-manno-hept-2-ulose (2) and two multivalent BSA-based structures 7 and 8, d-manno-configured C-glycosyl-type compounds derived from an Amadori rearrangement, were evaluated as ligands for mannoside-specific lectins of various sources. The determination of the concentration corresponding to 50% of inhibition (IC50) is described. Multivalency turned out to effectively influence ligand selectivity and lectin binding.
Assuntos
Antibacterianos/farmacologia , Lectinas/farmacologia , Manosídeos/farmacologia , Amaryllidaceae/efeitos dos fármacos , Antibacterianos/química , Burkholderia/efeitos dos fármacos , Canavalia/efeitos dos fármacos , Galanthus/efeitos dos fármacos , Lectinas/síntese química , Lectinas/química , Ligantes , Manosídeos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Vicia/efeitos dos fármacosRESUMO
The Amadori rearrangement was investigated for the synthesis of C-glycosyl-type neoglycoconjugates. Various amines including diamines, amino-functionalized glycosides, lysine derivatives, and peptides were conjugated with two different heptoses to generate non-natural C-glycosyl-type glycoconjugates of the d-gluco and d-manno series. With these studies, the scope and limitations of the Amadori rearrangement as a conjugation method have been exemplified with respect to the carbohydrate substrate, as well as the amino components.
RESUMO
The Amadori rearrangement was employed for the synthesis of C-glycosyl-type D-mannoside analogues, namely 1-propargylamino- and 1-phenylamino-1-deoxy-α-D-manno-heptopyranose. They were investigated as ligands of type 1-fimbriated E. coli bacteria by means of molecular docking and bacterial adhesion studies. It turns out that Amadori rearrangement products have a limited activity as inhibitors of bacterial adhesion because the ß-C-glycosidically linked aglycone considerably hampers complexation within the carbohydrate binding site of the type 1-fimbrial lectin FimH.