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Updated: May 22, 2025

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
Unlocking Enol-Ugi-Derived Conformationally Restricted Peptidomimetic Motifs
José Luis Ramiro1, Jesús Díaz1, Ana G Neo1
1Laboratory of Bioorganic Chemistry & Membrane Biophysics (L.O.B.O.). Departamento de Química Orgánica e Inorgánica, Universidad de Extremadura, Cáceres 10003 Spain.
Abstract:
The enol-Ugi condensation, a versatile multicomponent reaction, provides a rapid and efficient route to enamine peptidomimetics. In this study, we investigated the factors influencing the conformational behavior of three enol-Ugi adducts with distinct structural features. Through DFT calculations and NCI analysis, we identified that noncovalent interactions, including hydrogen bonds and π-π interactions, play a pivotal role in restricting conformational flexibility. While six-membered cyclic enamines 6 and 7 exhibited varying degrees of rotational freedom, the indanone-derived enamine 8 displayed a locked conformation resembling a retropeptidic turn. These findings highlight the potential of tailoring enol-Ugi adducts to mimic biologically relevant peptidic motifs, opening new avenues for drug discovery and design.
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