Selective Recognition of β‐Mannosides by Synthetic Tripodal Receptors: A 3D View of the Recognition Mode by NMR

Abstract

Unravelling the structural features of carbohydrate recognition by receptors is a topic of major interest. In recent years, several synthetic receptors capable of binding different sugars with moderate to good affinities and selectivities have been developed. Here we report on the analysis of the three‐dimensional structures of the complexes of two recently derived synthetic tripodal receptors with octyl β‐D‐mannopyranoside, a monosaccharidic glycoside selectively recognized in a polar solvent, by a combination of NMR methods and assisting molecular mechanics calculations. The variations in the chemical shifts upon complexation and the observed intermolecular NOEs were employed to validate the molecular‐mechanics‐derived structures. The structures of the obtained complexes explain the observed mannose selectivity in chemical terms, suggesting that a combination of van der Waals, CH–π and hydrogen‐bonding forces are involved in the formation of the complexes, together with stabilizing conformational effects of the substituents.

Biomimetic Carbohydrate‐Binding Agents (CBAs): Binding Affinities and Biological Activities

“…Prompted by their similar mannose‐binding properties, in a pioneering study we have explored the potential of our aminopyrrolic tripodal receptors as antimicrobial agents . In a preliminary screening, the progenitor of the family, compound 9 , and the most effective mannose receptors 16 and 17 were tested towards yeast and yeast‐like pathogenic target strains of Candida tropicalis , Pichia norvegensis , Prototheca wickerhamii and Prototheca zopfii . The minimum inhibitory concentrations (MICs) reported in Table clearly show that all compounds markedly inhibit the growth of the four microorganisms; in particular, the MIC values of 9 were closely comparable to those of well‐known antibiotics such as amphotericin B (AmB) and ketoconazole (Keto).…”

Carbohydrate force fields

“…The procedure yielded 99 papers124–222 in which a classical FF, which was not necessarily a CarbFF, was applied to a carbohydrate. Studies that considered only DNA or RNA were excluded.…”

Molecular architecture and therapeutic potential of lectin mimics

“…21) of compound 44 were less active or inactive, indicating that all structural components are essential for antimicrobial activity. Analogues of 44 were also prepared, and representative examples (88)(89)(90)(91)(92) are shown in Fig. 22.…”

“…22. Antimicrobial assay using a variety of yeast and yeast-like microorganisms revealed that none of the modifications, including introduction of functional groups into the pyrrole rings (88-90) and variation of substitution pattern on the benzene platform (91,92), enhanced the activity of the parent compound 44 (Table X). The binding affinity of these compounds for Oct-a-Man was also evaluated in acetonitrile.…”

“…90; d Measured in CD 3 CN; e Data cited from Ref. 91.calculations suggested that this notable selectivity of 45 for Oct-b-Man was derived from a conformational restriction induced by the cyclic acetal substituents on the pyrrole unit 92. The resulting narrower binding-cleft of 45 fits preferentially to Oct-b-Man.…”