Ac10c: a medium‐ring,cycloaliphatic Cα,α‐disubstituted glycine. Incorporation into model peptides and preferred conformation |
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Authors: | A Moretto F Formaggio M Crisma C Toniolo M Saviano E Benedetti R Iacovino RM Vitale |
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Abstract: | Abstract: Two complete series of N‐protected oligopeptide esters to the pentamer level from 1‐amino‐cyclodecane‐1‐carboxylic acid (Ac10c), an α‐amino acid conformationally constrained through a medium‐ring Cαi ? Cαi cyclization, and either the l ‐Ala or Aib residue, along with the N‐protected Ac10c monomer and homo‐dimer alkylamides, were synthesized using solution methods and fully characterized. The preferred conformation of these model peptides was assessed in deuterochloroform solution using FT‐IR absorption and 1H NMR techniques. Furthermore, the molecular structures of two derivatives (Z‐Ac10c‐OH and Fmoc‐Ac10c‐OH) and two peptides (the dipeptide ester Z‐Ac10c‐l ‐Phe‐OMe and the tripeptide ester Z‐Aib‐Ac10c‐Aib‐OtBu) were determined in the crystal state using X‐ray diffraction. The experimental results support the view that β‐bends and 310‐helices are preferentially adopted by peptides rich in Ac10c, the third largest cycloaliphatic Cα,α‐disubstituted glycine known. This investigation allowed us to complete a detailed conformational analysis of the whole 1‐amino‐cycloalkane‐1‐carboxylic acid (Acnc, with n = 3–12) series, which represents the prerequisite for our recent proposal of the ‘Acnc scan’ concept. |
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Keywords: | β ‐bend cyclic amino acid 310‐helix peptide synthesis spectroscopy X‐ray diffraction |
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