De Novo Design and Synthesis of Helix–Turn–Helix Structure from Short and Robust Mixed Helices Derived from C‐Linked Carbo‐β‐Amino Acids

Abstract

In a twist: Tethering of short peptides with robust 10/12‐mixed helices, derived from C‐linked carbo‐β‐amino acids, to the turn‐inducing motif, β‐hGly‐D‐Pro‐Gly‐β‐hGly, permitted a de novo design of the helix–turn–helix motif in the foldamer domain.

Chirality and Template‐Mediated Induction of Helical Preferences in Achiral β‐Peptides

“…The above facts, as well as several discrete medium‐range nOe correlations [for example, CβH(1)( pro‐R )/CαH(3)( pro‐R ), CβH(1)( pro‐R )/NH(3), CβH(3)( pro‐R )/NH(5), CβH(3)( pro‐R )/CαH(5)( pro‐R )], along with sequential correlations CβH(1)( pro‐R )/NH(2), CαH(1)( pro‐S )/NH(2), NH(2)/CαH(3)( pro‐R ), CαH(2)( pro‐R )/NH(3), CβH(3)( pro‐R )/NH(4), CαH(3)( pro‐S )/NH(4), NH(4)/CαH(5)( pro‐R ), CαH(4)( pro‐R )/NH(5), and NH(4)/NH(5), provide emphatic support for the presence of a 12/10‐helix 26. 28 These findings are very important; they not only provide unmistakable evidence for the induction of a helical preference in achiral peptides, but also provide the first unequivocal experimental proof for the theoretically predicted preference for the 12/10‐helix in β‐peptides in apolar solvents 20. 21…”

“…Synthesis of peptides 12 – 15 and 29 – 32 : Peptide coupling of acid 20 a with salt 25 (prepared by tert ‐butoxycarbonyl (Boc) deprotection of 3 ) afforded dipeptide 26 (88 %). Base hydrolysis [4 n NaOH (aq)] of ester 26 gave acid 26 a , which furnished tripeptide 12 (87 %) on peptide coupling with salt 20 28. Further peptide coupling of acid 16 with salt 27 a gave tetrapeptide 28 (71 %), which afforded salt 28 a after treatment with CF 3 COOH in CH 2 Cl 2 .…”

“…The above results indicate the role of chiral induction by a carbohydrate residue, but also open up several possibilities. To investigate further, peptide 8 with a C‐terminal ( R )‐β‐Caa residue26, 28 (a β‐amino acid with a carbohydrate side chain) was synthesized and investigated. The 1 H NMR spectrum of 8 displayed diastereotopicity for the methylene protons of all of the β‐hGly residues.…”

“…Based on the findings on the induction of helicity/screw sense2, 4–7, 9–12 in achiral oligomers and the behavior of β‐hGly, it was proposed that β‐hGly oligomers, which do not reveal well‐defined structures, could be persuaded to have helical folding. Thus, we planned to adopt the strategy of end capping the β‐peptide oligomers formed from β‐hGly, either with a chiral amino acid (β‐Caa)27 residue or with a robust template28 derived from β‐Caas (Figure 1), at the peptide termini to stimulate a secondary structure. This philosophy of anchoring the termini by two helical fragments was also adopted by Huc et al 29.…”

Recognition of a Flipped Base in a Hairpinloop DNA by a Small Peptide

“…In many of the double stranded DNA binding proteins with helix-turn-helix, leucine zipper, Zn finger, or other minor motifs, [1][2][3] the principal determinants of specificity are hydrogen bonds involving functional groups of bases at the grooves in the helical DNA structure. On the other hand, for binding to RNA, proteins recognize their target RNAs via various recognition modes.…”