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Self-Organization Ability of Chiral Nα‑Substituted, Nβ‑Boc Protected α‑Hydrazinoacetamides in the Crystal and Solution States

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posted on 29.08.2017, 00:00 authored by Ralph-Olivier Moussodia, Eugénie Romero, Emmanuel Wenger, Brigitte Jamart-Grégoire, Samir Acherar
The limitations of peptides have severely hampered their use in pharmacology, thus prompting the design of new peptidomimetic foldamers. This requires precise knowledge of the secondary structure of new compounds and the ability to predict their folding. Conformational studies of the basic units of these foldamers can be of invaluable assistance in designing new bioactive compounds. To this end, we investigated the conformation of three chiral Nα-substituted, Nβ-Boc protected α-hydrazinoacetamide model compounds containing various side chains both on the Nα- and Cα-atoms in both the crystal and solution states. On the basis of IR absorption spectroscopy, NMR, molecular dynamics calculations and X-ray diffraction experiments, we demonstrated that these three models adopt conformational preferences, relying on eight-, six- or five-membered H-bonded pseudocycles (C8, C6 or C5), depending on the steric bulk of both Nα- or Cα-side chains. This study sheds light onto the versatile folding ability of the specific class of α-Nα-hydrazinopeptides and emphasizes the key role of the Cα-side chain on the conformational preference of the folding.