Chemical communication: conductors and insulators of screw-sense preference between helical oligo(aminoisobutyric acid) domains

Abstract

(1)H NMR studies quantify the abilities of achiral amino acids to communicate a left-handed screw-sense preference from one helical Aib(4) domain to another: certain quaternary amino acids (e.g. Ac(6)c) act as effective conductors of conformational preference while others (e.g. diphenylglycine) acts as insulators.

Participation of non-aminoisobutyric acid (Aib) residues in the 310helical conformation of Aib-rich foldamers: a solid state study

“…The achiral quaternary residues, Ac 5 c, Ac 6 c and Bip, were selected as they have been previously studied in solution and shown to perform as effective conductors of conformational preference in long Aib oligomers. 17 Furthermore, our solutionbased studies have demonstrated that these residues give levels of stereochemical control comparable to those achieved with Aib residues. 17,22 The efficiency of chirality transfer achieved by the achiral quaternary amino acids, Ac 5 c, Ac 6 c and Bip, as determined by NMR spectroscopy, implicated the adoption of a global stable 3 10 helical conformations in solution despite the presence of these non-Aib residues.…”

“…17 Furthermore, our solutionbased studies have demonstrated that these residues give levels of stereochemical control comparable to those achieved with Aib residues. 17,22 The efficiency of chirality transfer achieved by the achiral quaternary amino acids, Ac 5 c, Ac 6 c and Bip, as determined by NMR spectroscopy, implicated the adoption of a global stable 3 10 helical conformations in solution despite the presence of these non-Aib residues. Ac 5 c and Ac 6 c residues can induce folding and the conformational preferences of these residues are known to support either 3 10 /a-helices in synthetic oligomers.…”

Sequence Engineering to Control the Helix Handedness of Peptide Foldamers

“…[36] The signal decay is faster at higher temperature and in polar solvent, andi td epends on the nature of the achiral oligomers in the chain.H owever,h elix persistence in non-polar solvents may exist for approximately 200 monomers. [37] Straightforward and effective observation of the P and M helices content by NMR is possible by incorporationo fs tereoselectively deuterated glycine [35,37,38] or Aib residues containing one 13 Cm ethyl group. [27] Thism ethod allows studies on influence of variousf actors on helix handedness including covalent modifications as well as interactions with other molecules.…”

The N‐Terminal Nonapeptide of Cephaibols A and C: A Naturally Occurring Example of Mismatched Helical Screw‐Sense Control

“…Peptide chains of achiral amino acids, even though they contain no asymmetric centres, may be induced into either a left-or a right-handed helical conformation by an external chiral influence. For example, homo-oligomers of the helicogenic [1][2][3] quaternary amino acid Aib [4,5] (2-aminoisobutyric acid), or hetero-oligomers of Aib and other achiral residues (such as Gly, [6][7][8] Ac6c, [8][9][10] or dehydroamino acids [9,11] ), may be induced to adopt a preferred screw sense by chiral residues bonded either covalently [6,[8][9][10][11][12][13] or non-covalently [13,14] at their N or C terminus. A remarkable naturally occurring achiral peptide motif of this type occurs towards the N-terminus of the antibiotic fungal metabolites cephaibol A, C, D and E (Figure 1).…”