Peptidomimetic secondary

Whereas peptidomimetics are sometimes taken to include all types of peptide analogues discussed in this Sect. 6.6, we restrict the term to two types of compounds. The first type includes moieties that mimic some elements of secondary structure, whereas the second type of peptidomimetics are mimics of a peptide s pharmacophore. 

This volume brings together most of these critical issues by highlighting recent advances in a number of core areas of peptidomimetic synthesis. Section 9 focuses on side-chain-modified peptides, Section 10 describes the preparation and use of a variety of peptide main-chain modifications. Combined side-chain- and main-chain-modified peptides are covered in Section 11. Finally, Section 12 provides chemistry leading to peptides incorporating secondary structure ((1- and y-turns, helices, p-sheets) mimetics and inducers. 

Molecular modeling calculations using ab initio methods (MP2/6-31+G ) predict that spiro-(3-lactam of type M adopt a (3-tum secondary structure [50] which is very close to the ideal type-III (3-tums. Thus, these spiro-(3-lactams are the important members of the core for the preparation of different types of peptidomimetics using well-established chemistry. They combine the structural features required for inducing (3-tum motif. 

Bradley developed a solid-phase synthesis of peptidomimetic dendrimers using the lysine-like peptoid monomer 25 [226] which led to G1-G3 dendrimers, bearing both primary and secondary amino groups on the periphery, with promising transfection abilities and no toxicity [227] (see Fig. 25). 

Liskamp RMJ. Conformationally restricted amino acid and dipeptides, (non)peptidomimetics and secondary structure mimetics. Rec. Trav. Chim. Pays-Bas 1994 113 1-19. 

Fig. 4 Example of a three-step synthesis of a series of rather elaborated peptidomimetic compounds synthesized using straightforward reactions that can be easily automated in a fast parallel synthesis process. Methods (a) acetic acid, poly-phosphoric acid, 85°C (b) RI, DMF, anhydrous potassium carbonate, room temperature (c) Willgerodt-Kindler reaction (sulfur, secondary amine HNAB, DMF, 110°C).

There is increasing interest in the development of foldamers or polymeric structures that can adopt organised secondary structures like those of proteins, nucleic acids and some polysaccharides [42]. Sugar amino acid-based foldamer research has so far been primarily concerned with synthesis of polymers with secondary sfructural features. Such foldamers may find application as scaffolds for peptidomimetic development if they adopt turn, helical and strand sfructures observed for peptides or if derivatives can act as ligands for peptide receptors ... 

Our focus here is on peptidomimetic oligomers whose secondary structure has been well characterized. For some of these backbones, monomers and sequences giving rise to helical, extended (i.e., strand ), and turn conformations have been identified. These will be discussed in greatest detail. Other systems included in this section are considered either as potential foldamers or systems that have been discussed within the context of foldamer research but for which only limited information about their secondary structures is presently available. In these cases we will restrict our discussion to brief summaries. 

Maillard MC, Flom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, Varghese J (2007) Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta -secretase. J Med Chem 50 776-781... 

The term peptidomimetic typically refers to mimicry of a few adjacent residues in a peptide sequence, and this type of molecular design approach is unlikely to be relevant to most protein-protein interfaces, since binding typically involves structural features derived either from one large secondary structural element or two or... 

One need look no further than some of the recent reviews in peptide mimetic chemistry - to see the substantial impact of computational chemistry on this field. For example, the 1993 Symposium-in-Print edition of Tetrahedron, entitled Peptide Secondary Structure Mimetics, contains 19 articles by practitioners involved in peptide mimetic design. The majority of these articles include references to the use of some form of computational chemistry in the research effort. In addition, as a further indication of the commercial interest, even a recent patent dealt with the computational aspects of peptidomimetic design. 

R. M. J. Liskamp, Reel. Trav. Chim. Pays-Bas, 113, 1 (1994). Conformationally Restricted Amino Acids and Dipeptides (Non)Peptidomimetics and Secondary Structure Mimetics. 

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