The beta-bend ribbon spiral. Synthesis and conformational analysis in solution and in the crystal state of depsipeptides containing alpha-hydroxyisobutyric acid.
The synthesis and conformational analysis in solution (by FTIR absorption and 1H NMR) and in the crystal state (by X-ray diffraction) of three Hib-containing depsipeptides have been performed. In the crystal state Z-Aib-Hib-Aib-OMe is folded into a type-III beta-bend, while the conformation adopted by Z-Aib-Hib)2-Aib-OMe is a beta-bend ribbon spiral, characterized by two type-III beta-bends with Aib(1)-Hib(2) and Aib(3)-Hib(4) as corner residues, respectively. Both independent molecules in the asymmetric unit of t-Boc-L-Ala-Hib-L-Ala-OMe crystals are folded into a type-II beta-bend. For the Aib-Hib depsipeptides the conformation adopted in the crystal state is also that largely prevailing in solution, whereas for t-Boc-L-Ala-Hib-L-Ala-OMe the beta-bend conformation is significantly less populated in solution. A comparison is also made with: (i) the published crystal-state conformations of fully protected -(Aib)3-, -(Aib)5-, and -L-Ala-Aib-L-Ala- sequences and the beta-bend ribbon spiral generated by (Aib-L-Pro)n oligomers, and (ii) with the herewith described solution preferred conformation of Z-L-Ala-Aib-L-Ala-OMe. The possible use of Hib as an isosteric replacement for Aib in the design of conformationally constrained depsipeptides is briefly discussed.
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Biopolymer Research Centre, C.N.R., Department of Organic Chemistry, University of Padova, Italy.
Valle
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Bonora
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Toniolo
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Cavicchioni
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D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids / Q000737:chemistry; D004952:Esters; D005561:Formates / Q000737:chemistry; D006860:Hydrogen Bonding; D006885:Hydroxybutyrates / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions; D014961:X-Ray Diffraction
D000621:Aminoisobutyric Acids; D004952:Esters; D005561:Formates; D006885:Hydroxybutyrates; D009842:Oligopeptides; D012996:Solutions; C018241:carbobenzoxy chloride; C100049:2-aminoisobutyric acid; C008039:2-hydroxyisobutyric acid