Molecular Recognition by Macrocyclic Receptors

Abstract

Effective molecular recognition requires the precise alignment of binding groups on the receptor with chemical features on the substrate. In the past two years we have initiated a program aimed at the development of artificial receptors containing several recognition sites that are complementary with biologically-interesting molecules. This project was inspired by a lecture at the 4th IPMR in Lancaster by Professor W. Saenger in which he discussed the X-ray structure of the guanine-binding enzyme, ribonuclease T₁ [1]. This shows a guanine substrate bound into the active site by both hydrogen bonding to the peptide backbone and aromatic stacking to a tyrosine aromatic ring (Figure 1). The presence of two recognition interactions increases both the strength and specificity of substrate binding.