Physical Sciences and Mathematics Commons^™

Molecular Recognition Of Insulin By A Synthetic Receptor, Jordan M. Chinai, Alexander B. Taylor, Lisa M. Ryno, Nicholas D. Hargreaves, Christopher A. Morris, P John Hart, Adam R. Urbach

Chemistry Faculty Research

The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 × 10⁶ M⁻¹ and with 50−100-fold selectivity versus proteins that are much larger but lack an N-terminal aromatic residue, and with >1000-fold selectivity versus an insulin variant lacking the N-terminal phenylalanine (Phe) residue. The crystal structure of the …