Synthesis of Guanidinium-Derived Receptor Libraries and Screening for Selective Peptide Receptors in Water

Abstract

A library of "tweezer" receptors, incorporating a guanidinium "head group" and two peptide derived side arms has been prepared on the solid-phase using an orthogonally protected guanidinium scaffold 12. The library was screened with various tripeptide derivatives in an aqueous solvent system. A tweezer receptor 25 for the side chain protected tripeptide 19 was identified from the screening experiments. Receptor 25 was resynthesised and solution binding studies were carried out, which revealed that 25 binds to tripeptide 19 with K(a)=8.2 x 10(4) +/- 2.5 x 10(4) (15 % DMSO/H(2)O, pH 8.75) and with appreciable selectivity over the tripeptide enantiomer 22 and the side chain deprotected tripeptide 20.