jo5b01668_si_001.cif (17.2 kB)
Cis–Trans Conformational Analysis of δ‑Azaproline in Peptides
dataset
posted on 2015-11-06, 00:00 authored by Indranil Duttagupta, Debojyoti Misra, Sourav Bhunya, Ankan Paul, Surajit SinhaThe cis–trans isomerization
and conformer specificity of
δ-azaproline and its carbamate-protected form in linear and
cyclic peptides were investigated using NMR and α-chymotrypsin
assay. Comparisons of the chemical shift value of the α-hydrogen
in each case of δ-azaproline-containing peptides with conformer-specific
locked diketopiperazines reveal the fact that an upfield chemical
shift value corresponds to cis conformer and a downfield value corresponds
to a trans conformer. δ-Azaproline adopts cis-conformation in
simple amides, dipeptides, and tripeptides whereas its carbamate-protected
form adopts trans-conformation. In the case of longer, linear or cyclic
peptides, vice versa results are obtained. Interestingly, in all these
peptides exclusively one conformer, either cis or trans, is stabilized.
This cis–trans isomerization is independent of both temperature
and solvents; only the δ-nitrogen protecting group plays key
role in the isomerization. δ-Azaproline is conformer-specific
in either of its protected or deprotected forms, which is a unique
property of this proline. Unlike other covalently modified proline
surrogates, this isomerization of δ-azaproline can be tuned
easily by a protecting group. The mechanism of cis–trans isomerization
of δ-azaproline during deprotection and reprotection is supported
by theoretical calculations.