Experimental investigations on the backbone folding of proline‐containing model tripeptides

AbstractSome proline‐containing tripeptides with the general formulas R0CO‐L‐Pro‐X‐NHR3 (X = Gly,Sar,L‐Ala,D‐Ala) and R0CO‐X‐L‐Pro‐NHR3 (X = Gly,L‐Ala,D‐Ala) have been investigated in solution by ir and 1H‐nmr spectroscopies. Their favored conformational states depend mainly on both the primary structure and the chiral sequence of the molecules. In inert solvents the βII‐folding mode is the most favored conformation for the L‐Pro‐D‐Ala and L‐Pro‐Gly tripeptides, while the βII′‐turn is largely preferred by D‐Ala‐L‐Pro derivatives. Under the same conditions only about one‐third of the whole conformers of L‐Pro‐L‐Ala molecules adopts the βI‐folding mode. Semiopened C7C5 and C5C7 conformations are appreciably populated in the L‐Pro‐L‐Ala sequence, on the one hand, and in the Gly‐L‐Pro and L‐Ala‐L‐Pro derivatives, on the other hand. In L‐Pro‐Sar and X‐L‐Pro models, the cis–trans isomerism around the middle tertiary amide function is observed. Thus cis L‐Pro‐Sar and L‐Ala‐L‐Pro conformers are folded by an intramolecular i + 3 → i hydrogen bond, whereas cis D‐Ala‐L‐Pro and Gly‐L‐Pro molecules accommodate an open conformation. In dimethylsulfoxide the βII‐ and βII′‐folding modes are not essentially destabilized, as contrasted with the βI conformation, which is less populated. In water solution all the above‐mentioned conformations, with the possible exception of the βII′‐folding mode for D‐Ala‐L‐Pro molecules, seem to vanish. Solute conformations are also compared with the crystal structures of four proline‐containing tripeptides.