Synthesis and Evaluation of Oligomeric Thioether-Linked Carbacyclic ?-(1?3)-Glucan Mimetics.

ABSTRACT: Extrapolating from lessons learnt with previous low-molecular-weight ?-(1?3)-glucan mimetics, we designed a series of minimal 2,4-dideoxy-thioether-linked carbacyclic ?-(1?3)-glucan mimetics and synthesized di-, tri-, and tetramers in an enantiomerically pure form by an iterative sequence based on a simple building block readily available from commercial ( S)-(-)-3-cyclohexenecarboxylic acid. These substances were screened for their ability to inhibit anti-CR3-fluorescein isothiocyanate (FITC) staining of human neutrophils and anti-Dectin-1-FITC staining of mouse macrophages as well as for their ability to stimulate phagocytosis and pinocytosis. In each assay, the synthetic compounds displayed comparable activity to the corresponding native ?-(1?3)-glucans, laminaritriose, and tetraose, suggesting that the exploitation of hydrophobic patches in the lectin-binding domains of CR3 and Dectin-1 is a promising strategy for the development of small-molecule analogues of ?-(1?3)-glucans.

SUBMITTER: Wen P 

PROVIDER: S-EPMC6528479 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature