Synthesis of Unsymmetrical Tweezer Receptor Libraries and Identification of Receptors for Lys-D-Ala-D-Ala in Aqueous Solution

• Published in: Chemistry : a European journal Vol. 12; no. 3; pp. 713 - 720
• Main Authors: Shepherd, Jon, Gale, Tom, Jensen, Kim B., Kilburn, Jeremy D.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 11-01-2006; WILEY‐VCH Verlag
• Subjects: Amino Acid Sequence; Combinatorial Chemistry Techniques; library; Oligopeptides - chemistry; peptides; receptors; solid-phase synthesis; Structure-Activity Relationship; Water - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200500876

Libraries of “unsymmetrical” tweezer receptors, featuring a guanidinium head group as a carboxylate binding site and two independently synthesized peptidic arms, have been prepared and screened to identify receptors for the N‐Ac‐Lys‐D‐Ala‐D‐Ala tripeptide sequence. The binding properties of one such receptor structure, with dye‐labeled N‐Ac‐Lys‐D‐Ala‐D‐Ala, were investigated. These studies demonstrated that when attached to the solid‐phase, the receptor binds dye‐labeled N‐Ac‐Lys‐D‐Ala‐D‐Ala, in buffered aqueous media, with mM binding affinity.
How to be a more receptive host! Independent, randomized synthesis of the two arms of a “tweezer” receptor library increases its structural diversity. This strategy has been used to identify a new receptor for the tripeptide N‐Ac‐Lys‐D‐Ala‐D‐Ala (see scheme).