Physical Sciences and Mathematics Commons^™

Nanomolar Binding Of Peptides Containing Noncanonical Amino Acids By A Synthetic Receptor, Leigh A. Logsdon, Christopher L. Schardon, Vijayakumar Ramalingam, Sharon K. Kwee, Adam R. Urbach

Chemistry Faculty Research

This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20–30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium dissociation constant (K_d) value of 0.95 nM in neutral phosphate buffer. Structure–activity studies revealed that three functional groups …