Pseudopeptidic macrocycle

Figure 24 Scheme of a membrane nanotube acting as an ion channel and structure of (a) S-peptides, (b) 5-peptides, (c) a,y-peptides, showing a substituent at C2 (R) to functionalize the corresponding nanotube, (d) a.e-peptide hybrid, (e) malonic acid-derived peptide, (f-i) cychc ureas, and Q) pseudopeptidic macrocycles. 

Alfonso I, Buiguete MI, Galindo F et al (2009) Unraveling the moleeular recognition of amino acid derivatives by a pseudopeptidic macrocycle ESI-MS, NMR, fluOTescence, and modeling studies. J Org Chem 74 6130-6142... 

This review will focus on the use of MCR approaches to cyclic peptides, cyclic peptidomimetics, or cyclic pseudopeptides, including small or medium-sized heterocycles as mimics of peptide motifs and macrocycles with amino acid or peptide moieties. 

These complex macrobicycles were assembled by the incorporation of eight more building blocks, forming 12-24 new bonds in a one-pot reaction. The more complex three-dimensional multi-macrocyclic pseudopeptides like the igloos might in principle be considered mimics of internally disulfide bridged crumpled proteins like the knottins (Scheme 27) [101]. 

Cousins, G.R.L., Poulsen, S.-A., Sanders, J.K.M. Dynamic combinatorial libraries of pseudopeptide hydrazone macrocycles. Chem. Commun. 1999, 1575-1576. 

They can be classified in two main classes (poly)macrocyclic molecules (e.g. vinblastine) and (mostly linear) pseudopeptides (e.g. dolastatin 10). Some ligands (e.g. phomopsin) have characteristics of both classes (Fig. 5). Whether the tubulin binding sites of these widely diverse molecules overlap or not remains to be established. Whatever the case, taken together these sites define the tubulin vinca domain [43]. 

Previous reviews on peptidomimetics have addressed pseudopeptides (11), macrocyclic mimetics (13), natural product mimetics (14), cyclic protease inhibitors (15), mimetics for receptor ligands (16-22), and earlier general overviews (23-29). This review will focus on the design process itself. Novel peptidomimetics in which the structural relationship between parent peptide and the peptidomimetic has been established by biophysical methods are used to clarify the principles. Successful approaches are highlighted to illustrate how these concepts are currently used. 

Figure 3.12 Chiral phosphoric acid derivative and macrocyclic pseudopeptide carriers.

Miyake, H., Yamashita, T., Kojima, Y., Tsukube, H. (1995). Enantioselective transport of amino acid ester salts by macrocyclic pseudopeptides containing N,N -ethylene-bridged-dipeptide units. Tetrahedron Lett., 36, 7669-72. 

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