Combinatorial solid-phase synthesis and screening of a diverse tripodal triazacyclophane (TAC)-based synthetic receptor library showing a remarkable selectivity towards a d-Ala-d-Ala containing ligand

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

“…Recently, Schmuck has used linear peptides, capped with a guanidinopyrrole as a carboxylate binding site, to identify receptors that bind the amyloid peptide (Val‐Val‐Ile‐Ala) in aqueous solution 2c,d. 6 Although not incorporating a specific carboxylate binding site, libraries of three‐armed receptors, based on a cyclotriveratrylene scaffold, have also been screened by Liskamp who utilized the dye‐labeled dipeptides D ‐Ala‐ D ‐Ala and D ‐Ala‐ D ‐Lac, with a free carboxylate terminus, as substrates in phosphate buffer 2a,b. These developments demonstrate the potential of such receptor systems to provide potent and sequence selective peptide receptors for use as novel therapeutics or biosensors.…”

Synthesis and Evaluation of TAC‐Based Inhibitors of Papain as Mimics of Cystatin B

“…[13][14][15] The TAC scaffold was designed in such a way that solid-phase chemistry was possible by attachment of the carboxylic acid moiety to a suitable resin. [13][14][15] In the synthesis approach, the Fmoc-protecting group was cleaved with piperidine (20 %) in N-methyl pyrrolidone (NMP) to liberate a secondary amine, which was decorated with a peptide chain. Next, the o-nitrobenzenesulfonyl An approach for mimicking protein-protein interactions by using a discontinuous epitope to construct a mimic that is about one tenth of the size of a natural inhibitor of papain, namely, cystatin B, is described.…”

“…In addition, the nonscaffolded peptides H-6 NleNleCysGlyAla 10 -NH 2 (13), Ac-53 GlnValValAlaGlyThr 58 -NH 2 (12), and Ac-122 LeuThrTyrPhe 125 -OH (14) were synthesized by means of standard Fmoc/tBu SPPS in order to evaluate the benefits of the TAC scaffold for preorganizing the peptide segments, as opposed to merely mixing the individual peptide components (Scheme 2).…”

Towards a New SPE Material for EDCs: Fully Automated Synthesis of a Library of Tripodal Receptors Followed by Fast Screening by Affinity LC

“…When using scaffolded peptides, generally, molecular diversity is obtained by synthesising split‐and‐mix libraries. Screening can then be performed by adding a labelledligand and selecting the fluorescent or colouredbeads 10b,10c,12. By using such a combinatorial approach, it sometimes remains difficult to establish the identity of the active compound, a process that is often complicated by the low amount of product synthesised 13.…”