In short oligopeptides, positioning of a central DPro-Gly segment has been shown to facilitate registry of N- and C-terminus strand segments, promoting an isolated hairpin . Extensive studies of apolar oligopeptides containing
DPro-Xxx segments have demonstrated hairpin formation in solution by NMR methods and X-ray diffraction in crystal structures . In the vast majority of cases of b-hairpin crystal structures, the DPro-Gly sequence adopts a type II ' b-turn conformation. In almost all the cases, three cross-strand hydrogen bonds are observed, with fraying at the N and C termini, resulting in the absence of the fourth hydrogen bond in some structures. Figure 5.9 provides examples of crystallographically determined structures of designed b-hairpins. Tables 5.1 and 5.2 summarize the available experimental evidences for hairpin formation in synthetic sequences soluble in organic and aqueous solvents, respectively. When Xxx = LPro, an obligatory type II' b-turn is formed. Indeed, DPro-LPro sequences have been used to generate stable hairpins in a variety of biologically important
synthetic peptides. The b-hairpin conformation of a model octapeptide Boc-Leu-Phe-Val-DPro-LPro-Leu-Phe-Val-OMe (Fig. 5.10) has been established in solution by NMR  and X-ray diffraction in crystals [unpublished]. It is pertinent to note that the homochiral diproline segment has been advanced as a potent helix nucleating template , whereas centrally positioned heterochiral diproline segments strongly favor b-hairpin formation [34, 35]. When the DPro-LPro (heterochiral) sequence is placed at the amino terminus, consecutive b-turn (II'-I/III) formation is observed . In principle, the II'-I/III consecutive b-turn structure at the amino terminus of a peptide sequence can serve to initiate a helical fold.
A variety of residues can be accommodated at the i + 2 position in the central b-turn [33, 37]. In the strands, lengthening of the backbone by incorporation of b and g amino acids [32d-g] can occur without disrupting the hairpin structure. This feature is exemplified in Fig. 5.11.
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