Nmr investigation of CYCLO 7,10 [C 7 ,X 9 ,C 10 ,Nle 12 ] analogues of the α‐factor from saccharomyces cerevisiae

The cyclo 7,10 [Cys 7 ,Cys 10 ,Nle 12 ], cyclo 7,10 [Cys 7 , D ‐Ala 9 ,Cys 10 ,Nle 12 ], and cyclo 7,10 [Cys 7 , L ‐Ala 9 ,Cys 10 ,Nle 12 ] analogues of the α‐factor mating pheromone (WHWLQLKPGQPMY) of the yeast Saccharomyces cerevisiae were studied in DMSO/water (80 : 20) and aqueous solution by nmr spectroscopy. In addition, the cyclo 7,10 [Cys 7 , D ‐Val 9 ,Cys 10 ,Nle 12 ] α‐factor was examined in DMSO/water. Nuclear Overhauser effect (NOE) and NH d δ/ dT data indicate that the cyclo 7,10 [Cys 7 , D ‐Val 9 ,Cys 10 ,Nle 12 ] α‐factor adopts a type II β‐turn in DMSO/water and that the cyclo 7,10 [Cys 7 , D ‐Ala 9 ,Cys 10 ,Nle 12 ] ‐ and cyclo 7,10 ‐[Cys 7 , L ‐Ala 9 ,Cys 10 ,Nle 12 ] α‐factor analogues adopt type II and type I/III β‐turns, respectively, in both DMSO/water and aqueous solutions. In aqueous solution, residues 8 and 9 of the cyclo 7,10 [Cys 7 ,Cys 10 ,Nle 12 ] α‐factor appear to adopt at least two distinct conformations, one of these being identified as a type I/III β‐turn. In contrast, the cyclo 7,10 [Cys 7 ,Cys 10 ,Nle 12 ] α‐factor appears to adopt predominately a type II β‐turn in DMSO/water. Quantitative NOE measurements of the cyclo 7,10 [Cys 7 ,Cys 10 ,Nle 12 ]‐, cyclo 7,10 [Cys 7 , D ‐Val 9 ,Cys 10 ,Nle 12 ]‐, and cyclo 7,10 [Cys 7 , L ‐Ala 9 ,Cys 10 ,Nle 12 ] α‐factors in DMSO/water were used to derive three‐dimensional structures of the cyclo 7,10 [Cys 7 ,Pro 8 ,X 9 Cys 10 ] portion of these analogues. © 1994 John Wiley & Sons, Inc.