Tweezer receptor

A new chiral benzothiazine ligand 205 was synthesized by Harmata and co-workers <06JOC3650>. It could be converted into a chiral molecular receptor 207 in a simple way. This chiral species 207 could be used as a new class of chiral molecular tweezers. The synthesis of 205 commenced with the protection of the commercially available compound 202, which was then coupled with f7tj-sulfoximinc 77b using the one-pot, one-operation procedure <99AG(E)2419> affording enantiomerically pure benzothiazine 204. This was followed by deprotection to produce benzothiazine 205 in good yield. 

Bonnat, M. Bradley, M. Kilburn, J. D. The Solid Phase Synthesis of a Guanidinium Based Tweezer Receptor, Tetrahedron Lett. 1996,37,5409-5412. 

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... 

Molecular clips and tweezers are two closely related types of compound. Molecular tweezers represent a simple kind of receptor in which two guest-binding domains usually comprising flat,... 

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. 

An Example Ligand and Receptor Libraries Based on Guanidinium Tweezer Receptors... 

The C-exposed library L35c was screened for its binding affinity for the guanidinium-based, fluorescent tweezer receptor 9.135 (225), whose structure is reported in Fig. 9.50. The dansylated chains should have assured the fluorescent detection of beads containing ligand tripeptidic sequences, and a series of control experiments ruled out the possibility of significant, nonspecific interaction of the beads with the receptor or with the biological assay constituents. The assay conditions were carefully optimized, and around 7000 beads (seven library equivalents, complete representation of the library individuals) were incubated with 9.135. 

Figure 9.50 Structure of the guanidiniutn-based tweezer receptors 9.135 and 9.136.

Figure 9.51 Synthesis of the SP-encoded pool, guanidinium-based tweezer receptor library L36 and structure of the selection substrate 9.138.

Davidson, L. Blencowe, A. Drew, M. G. B. Freebaim, K. W. Hayes, W., Synthesis and evaluation of a solid supported molecular tweezer type receptor for cholesterol, J. Mater. Chem. 2003,13,758-766... 

The binding of various nucleobases by a molecular tweezer has been studied by Vogtle and coworkers [107]. They found that this receptor (Figure 81) bound 2,6-diaminopurine and adenine with of the order of 10 M . 2-Aminopurine, cytosine, guanine and 2,4-dihydroxypteridine did not show any observable binding. 

Figure 7.6. Molecular structures of the precursor (8) and the tweezer peptide library receptors (9, 10) based on P-sulfonopeptides.

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. 

Boyce et al. [85] designed a library of peptidosteroidal receptors. In this library, the arms of the tweezers were composed of different peptides with a steroid scaffold as joint... 

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