Recent experimental and theoretical data suggest that some amino acid residues in the unfolded state of peptides and proteins do not exhibit a statistical coil behavior in that they predominantly adopt polyproline II (PPII) like conformations. [1]. In order to determine the individual propensity of amino acids in the absence of nearest neighbor interactions we measured the 1H NMR spectra of a set of GXG peptides where X represents the 20 naturally occurring amino acids as well as isobutyric acid and determined the 3JCHNH coupling constants for the central X residue. The coupling constants are used as constraints in a simulation of the amide I band profile in the respective vibrational circular dichroism (VCD), IR, and anisotropic and isotropic Raman spectra, which were performed in terms of mixtures of different conformations representing PPII, Beta-strand, helical and turn like conformational ensembles. A successful reproduction of band profiles and 3JCHNH coupling constant yields the fractions of the different conformations sampled by the investigated residue at room temperature. ECD spectra of the peptides with non-aromatic side chains were measured as a function of temperature. They are diagnostic of a substantial population of PPII conformation at room temperature the amount of which is significantly side chain dependent. The intensity of the PPII-type couplet decreases with increasing temperature indicating a higher population of Beta-strand like conformations. Altogether, the data obtained thus far suggest that V, F, and Y prefer the Beta-strand region of the Ramachandran space whereas A exhibits a clear PPII propensity. K (charged), E, and M do not exhibit a clear structural preference and are more in line with expectations from a statistical coil model. The data for GFG suggests a structure different from the gamma-turn structure obtained for AFA.

[1] Sreerema, N.; Woody, R. W. Biochemistry 1994, 33, 10022.