Compatibility of β- and γ-Turn Features with a Peptide Backbone Modification: Synthesis and Conformational Analysis of a Model Cyclic Pseudopentapeptide

Article abstract of DOI:10.1021/ja00264a041

A backbone-modified cyclic peptide has been synthesized and characterized by carbon-13 and proton NMR spectroscopies, and the results have contrasted with well-defined parent all-amide model cyclic pentapeptide.The pseudopeptide was prepared by solid-phase methods using two different linear sequences and then cyclized to yield a common structure.When a mixture of diphenylphosphoryl azide, hydroxybenzotriazole, and (dimethylamino)pyridine was used, the yield of cyclization was 85percent.The pseudopeptide, cycloGly-D-Phe-Pro>, containing a single thiomethylene group as an amide bond surrogate was nevertheless able to adopt both β- and γ-intramolecular hydrogen bonds in deuteriochloroform, as assessed by diagnostic chemical shift, temperature dependence, and solvent dependence data.However, in contrast to its all amide counterpart, the cyclic pseudopeptide showed evidence of cis/trans-proline peptide bond isomerism upon addition of dimethyl sulfoxide.