Folding of a Linear Array of α‑Amino Acids within a Helical Aromatic Oligoamide Frame

Control of the spatial
organization of proteinogenic side chains
is critical for the development of protein mimics with selective recognition
properties toward target protein surfaces. We present a novel methodology
for producing a linear array of proteinogenic residues based on the
incorporation of α-amino acids into sequences of rigid, helically
folded oligoamides of 8-amino-2-quinolinecarboxylic acid (Q). When l-leucine (L) was alternated with dimer Q2, the resulting sequence adopted a right-handed
helical conformation, as deduced in solution from the CD spectra of l-(LQ2)n (n = 2, 4) and in the solid state from X-ray crystallographic
analysis of (±)-(LQ2)4. Each LQ2 segment spanned just one helix turn (pitch
of 3.5 Å), and consequently, the four leucine side chains of
(LQ2)4 formed a linear array. In
solution, NMR analysis showed that both l-(LQ2)2 and l-(LQ2)4 exist as a mixture of two slowly equilibrating folded
conformers, the proportion of which strongly varies with the solvent.