Tweezer-like receptors

The concept of tweezer-like two-armed molecules was used to construct synthetic receptor molecules based on methylene sulfonamide peptidomimetics.11291 When screened for binding against an encoded tripeptide library, one of the synthetic receptors demonstrated a remarkable binding selectivity 11291 the synthetic receptor affinity could be further increased by varying the hinge part of the peptidomimetic molecule.11301... 

The tweezer-like compound 44 was reported as another receptor for peptides [74]. This study incubated a 1,000-member library of resin-bound tripeptide guests with the dansylated receptor. After washing, the beads were examined for fluorescence, and approximately 3% of the library was found to bind the host. A 95% selectivity for Val-C-terminating peptides was observed as well as a 40% selectivity for t-BuO-Glu in the central position of the tripeptide. A binding constant of 4xl05 M"1 for their best binder was determined by ITC. A reverse experiment with a resin-bound receptor and free tripeptides was attempted, but no significant binding was observed. 

On the basis of this concept, Gennari et al. [83] and Lowik et al. [84] developed tweezers-like , two-armed synthetic receptors made of peptidesulfonamides as peptidomimet-ics. Their aim was to investigate the affinity of libraries of these tweezers-like receptors to peptides or other biomolecules. The structure of a two-armed receptor, which is shown in Figure 10.6, consists of three areas First, there is a joint unit to which the arms of the tweezers are connected then, a dye molecule or a resin bead is attached to the joint unit and finally, there are the two arms of the tweezers which carry peptidic or peptidomimetic interaction sites. If a ligand with a chromophore has bound to this receptor, the colored resin beads can be selected and characterized. 

A tweezer-like receptor with arms derived from amino acids adjoined through a guanidinium group is... 

In more recent work, Greenland, Colquhoun, Cardin and co-workers produced a supramolecular receptor that contains both D and A components two pyrenyl residues and a single NDI residue (4, Fig. 8) [50]. The receptor was designed such that the separation of the pyrenyl resides is 7 A, which allows formation of a tweezer -like complex with the ir-electron-deficient NDI residue of a second component. The solid-state stmcture of this system reveals that a dimeric complex is formed with a suprastmcture reminiscent of a Roman handshake (Fig. 4a). One-... 

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