Pseudopeptides, cyclic

Y. Crozet, J. J. Wen, R. O. Loo, P. C. Andrews, A. F. Spatola, Synthesis and Characterization of Cyclic Pseudopeptide Libraries Containing Thiomethylene and Thiomethy-lene-sulfoxide Amide Bond Surrogates , Mol. Discov. 1998, 3, 261-276. 

Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions... 

The combination of pept(o)id-introducing MCRs with subsequent and efficient post-condensation transformations, especially ring-closing protocols, is an efficient concept to produce (cyclic) pseudopeptides. The most important versions make use of protected or convertible functional building blocks to allow later condensation, specially cycfization. Most relevant are Ugi-deprotection-cyclization (UDC), Ugi-activation-cyclization (UAC), and the Ugi-deprotection-activation-cycfization (UDAC), which take advantage of the diverse functionalities incorporated into the previously synthesized MCR-adduct as bi- or polyfunctional building block (Fig. 3) [15, 16]. 

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. 

The respective association constants of the latter anion to free 376 is only 10 M 1 while for the self-assembled complex it is equal to 2.5 104 M 1 [39]. Kubik and Goddard obtained a cyclic pseudopeptide ditopic receptor 378 for the simultaneous complexation of cations and anions [40]. Simultaneous encapsulation of N03 and PF6 ions by a highly charged (+12) anion receptor 379 was achieved by Schnebeck and coworkers [41]. By coordinating of 2,4,6-tris[(4-pyridyl)methylsulfa nyl]-l,3,5-triazine 380 with Ag, Hong and coworkers obtained nanosized tubes (Fig.7.8.1) that could host solvent and anionic molecules [42]. 

Peptide cyclization significantly reduces this flexibility, as shown by model studies with cyclic pseudodipeptides. When incorporated into biologically active cyclic peptides, potencies are generally retained or even enhanced. But flexibility is still a feature since pseudopeptide analogues of the p-receptor-selective opioid parent peptide, Tyr-c[-D-Lys-Gly-Phe-Leu-], were potent but nonselective with respect to activity toward p- and 6-re-ceptorsJ50]... 

Another type of template is based upon cyclic pseudopeptides in which three, four, five, or more units of alternating natural amino acids (e.g., Lys) and 3-aminobenzoic acid (Abz) are integrated into a cyclic structure, c[-Xaa-Abz-]n)65 66 ... 

Eight-membered A,iV -protected cyclic sulfonylamide 89, bearing two different protecting groups, was demonstrated as useful intermediate for preparation of pseudopeptides. Synthesis of 89 was carried out in two steps by an intermolecular Mitsunobu reaction followed by intramolecular N-alkylation (Scheme 20 <2003T6051>). 

DPPA-mediated cyclization was used for formation of 15-membered pseudopeptides 102 and 103 containing one <1997TL779> or two <1997TL3143> /rawr-cyclohcxanc-1,2-diamine fragments. The amidic groups were successfully reduced by LAH affording cyclic pentaamines 104 and 105 (Scheme 15). 

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. 

Mostly cyclic pseudopeptides from the lumpfish Do-labella auricularia (living in the Indian Ocean) with remarkable antitumor effects. The most important... 

Kubik, S. Goddard. R. A new cyclic pseudopeptide composed of (L)-proline and 3-aminobenzoic acid subunits... 

T 0 conclude this part on dynamic combinatorial chemistry, we will mention the use of a polymer bound N-methyl ammonium ion as a template. The library is generated from the pseudopeptide building block mPro, which gives a dynamic library of hydrazones (Fig. 23). Depending on the conditions, the following will be formed at equilibrium in the absence of a template, 85% of the cyclic dimer and 7% of the cyclic trimer in the presence of the template BTA, 47% of the dimer and 50% of the trimer and in the presence of the immobilized template. 40% of pure trimer can be isolated by washing the resin. 

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