Helical Mimetics side chains

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. 

The classical strategy to stabilize the ot-helical conformation in peptides employs covalent bonds between the i and i + 4 or i and i + 1 side-chain groups (Fig. 14). Earliest side-chain crosslinks utilized lactam, disulfide, and metal-mediated bridges [95-104]. Helices containing lactam-bridges and disulfide links have been shown to successfully target their intended receptors [100, 105-109]. While lactam crosslinks can improve the proteolytic stability of peptide mimetics, disulfide bonds are less desirable because they are chemically labile. 

Fig. 13 Stabilized helices and nonnatural helix mimetics several strategies that stabilize the a-helical conformation in peptides or mimic this domain with nonnatural scaffolds have been described. Recent advances include [1-peptide helices, terphenyl helix-mimetics, mini-proteins, peptoid helices, side-chain crosslinked a-helices, and the hydrogen bond surrogate (HBS) derived a-helices. Circles represent amino acid side-chain functionality (Reprinted from Henchey et al. [52], Copyright (2008) with permission from Elsevier)...

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