2 research outputs found
New Preorganized γ-Amino Acids as Foldamer Building Blocks
An asymmetric synthesis of two new diastereomeric γ-amino acids is described. Both molecules contain a cyclohexyl ring to limit conformational flexibility about the C<sub>α</sub>–C<sub>β</sub> bond; they differ in having <i>cis</i> vs <i>trans</i> stereochemistry on the ring. Residues derived from the <i>cis</i> γ isomer are shown to support helical secondary structures in α/γ-peptide oligomers
A γ‑Amino Acid That Favors 12/10-Helical Secondary Structure in α/γ‑Peptides
H-bonded helices in conventional
peptides (containing exclusively
homochiral α-amino acid residues) feature a uniform H-bonding
directionality, N-terminal side Cî—»O to C-terminal side NH.
In contrast, heterochiral α-peptides can form helices in which
the H-bond directionality alternates along the backbone because neighboring
amide groups are oriented in opposite directions. Alternating H-bond
directions are seen also in helices formed by unnatural peptidic backbones,
e.g., those containing β- or γ-amino acid residues. In
the present study, we used NMR spectroscopy and crystallography to
evaluate the conformational preferences of the novel γ-amino
acid (1<i>R</i>,2<i>R</i>,3<i>S</i>)-2-(1-<i>a</i>mino<i>p</i>ropyl)-<i>c</i>yclo<i>h</i>exanecarboxylic acid (APCH), which is constrained by a
six-membered ring across its Cα–Cβ bond. These
studies were made possible by the development of a stereoselective
synthesis of N-protected APCH. APCH strongly enforces the α/γ-peptide
12/10-helical secondary structure, which features alternating H-bond
directionality. Thus, APCH residues appear to have a conformational
propensity distinct from those of other cyclically constrained γ-amino
acid residues