Synthesis and Folding Propensity of Aliphatic Oligoureas Containing Repeats of Proline-Type Units

The
synthesis and conformational analysis of aliphatic oligoureas
containing multiple adjacent N-alkylated units derived
from proline (i.e., Prou) are reported. The insertion of
trisubstituted ureas in the main chain of N,N′-linked oligourea foldamers locally impairs the
characteristic three centered-hydrogen bonding pattern associated
with the formation of 2.5-helical structures. Three series of oligomers
have been studied: one series in which the Prou repeat
is flanked on both sides by canonical urea residues (e.g., oligomers 2–6), one series with canonical residues
on either side of the Prou repeat (oligomers 12 and 23), and one series consisting exclusively of Prou residues (oligomers 25 and 26).
Spectroscopic (NMR and electronic circular dichroism) and X-ray diffraction
studies reveal that the 2.5-helix formed by oligomers of N,N′-disubstituted ureas is robust enough
to accommodate short oligopyrrolidine segments (Prou)n (n < 7) that alone display
no intrinsic folding propensity.