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Abstract

For a comparison with the corresponding alpha- and beta-hexapeptides H-(Val-Ala-Leu)2-OH (A) and H-(beta-HVal-beta-HAla-beta-HLeu)2-OH (B), the corresponding gamma-hexapeptide (I), built from the homochirally similar (S)-4-aminobutanoate, (R)-4-amino-5-methylhexanoate, and (R)-4-amino-6-methylheptanoate, was prepd. The precursors were obtained either by double Arndt-Eistert homologation of protected Boc-Val-OH, Boc-Ala-OH, and Boc-Leu-OH, or by the superior route involving olefination/hydrogenation of the corresponding aldehydes, Boc-valinal, Boc-alaninal, and Boc-leucinal. Conventional peptide coupling (EDC/HOBt) furnished I through the intermediate gamma-di- and gamma-tripeptide. NMR measurements in (D5)pyridine and CD3OH soln. (COSY, TOCSY, HSQC, HMBC, ROESY) reveal that I adopts a right-handed helical structure [(P)-2.61 helix of .apprx.5-.ANG. pitch, contg. 14-membered H-bonded rings] which is to be compared with the left-handed helix of beta-peptide B [(M)-31 helix of 5-.ANG. pitch, 14-membered H-bonded rings] and with the familiar right-handed, so-called alpha-helix of alpha-peptides [(P)-3.61 helix of 5.4-.ANG. pitch, 13-membered rings]. Like the helix sense, the helix dipole reverses when going from alpha-(N->C) to beta-(C->N) to gamma-peptides (N->C). The surprising difference between the natural alpha-, and the analogous beta- and gamma-peptides is that the helix stability increases upon homologation of the residues.

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