β‐Turns in bridged proline‐containing cyclic peptide models

Abstract

Abstract The synthesis, CD, ir spectroscopic, and conformational studies of a series of bridged cyclic peptides of the general formula, cyclo [NH‐(CH 2 ) n ‐CO‐Gly‐Pro‐Y‐Gly] ( 2a – d , Y = Gly or Ser(OBu t ), n = 4 or 2) is reported. As indicated by difference nuclear Overhauser enhancement and Fourier transform ir experiments, the tetrapeptide sequence of cyclo [NH‐(CH 2 ) 4 ‐CO‐Gly‐Pro‐Gly‐Gly] ( 2a ) and cyclo [NH‐(CH 2 ) 2 ‐CO‐Gly‐Pro‐Gly‐Gly] ( 2b ) adopts a 1 ← 4 hydrogenbonded type II β‐turn conformation in solution, while cyclo [NH‐(CH 2 ) 4 ‐CO‐Gly‐Pro‐Ser(OBu t ) ‐Gly] ( 2c ) features a type I β‐turn, fixed by 1 ← 4 and O γ … NH intramolecular H bonds. In aqueous solution 2a and 2c show class B and class C CD spectra, respectively. This is the first case reported of a typical class C CD pattern in aqueous solution for a conformationally mobile system having a type I β‐turn. Based on the comparison of the band intensities of the bridged models with those of linear and cyclic model systems reported earlier, a set of subspectra with reduced band intensities is suggested for use in the CD analysis of the conformation of polypeptides in solution.