Bio-inspired synthetic receptor molecules towards mimicry of vancomycin.

A 512-member library of bio-inspired synthetic receptor molecules was prepared featuring a triazacyclophane scaffold. The purpose of this scaffold was to orient three (identical) peptide 'binding arms' in order to mimic an antibiotic binding cavity as is present in the vancomycin antibiotics. The library was screened with D-Ala-D-Ala and D-Ala-D-Lac containing ligands, which are present in the cell wall precursors of pathogenic bacteria. Screening and validation led to identification of a synthetic receptor capable of binding these ligands.

Simple and efficient preparation of [10,20-13C2]- and [10-CH3,13-13C2]-10-methylretinal: introduction of substituents at the 2-position of 2,3-unsaturated nitriles.

In this paper, we present the synthesis of [10,20-13C2]-10-methylretinal and [10-CH3,13-13C2]-10-methylretinal, two doubly 13C-labeled chemically modified retinals that have been recently used to study the structural and functional details behind the photocascade of bovine rhodopsin (Verdegem et al. Biochemistry 1999, 38, 11316; de Lange et al. Biochemistry 1998, 37, 1411). To obtain both doubly 13C-labeled compounds, we developed a novel synthetic method to directly and regiospecifically introduce a methyl substituent on the 2-position of 3-methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-2,4-pentadienenitrile. Encouraged by these results, we investigated the scope of this novel reaction by developing a general method for the introduction of a variety of substituents to the 2-position of 3-methyl-2,3-unsaturated nitriles, paving the way for simple and efficient synthesis of a wide variety of 10-, 14-, and 10,14-substituted chemically modified retinals, and other biologically important compounds.