Conformation of Peptides in Water

Abstract

Conformational aspects of small peptides have been studied extensively by both experimental [1, 2] and theoretical [3, 4] techniques. An understanding of these systems is important for the investigation of the folding of polypeptides and proteins since they should indicate the role of short-range interactions in stabilizing these larger structures. In this paper we shall describe and discuss the quantitative determination of the conformations in aqueous solution of a variety of short peptides through the use of the paramagnetic lanthanide cations as NMR probes. Previous experimental studies on peptide systems have been largely restricted to organic solvents and several of these have endeavoured to interpret the relative populations of different conformations of dipeptide derivatives by combining the spectroscopic data with theoretical calculations [1]. These reports have indicated that there are essentially two conformations (with dihedral angles Φ, ψ of –170°, 170° and –80°, 80° respectively) present in dilute carbon tetrachloride solution and that both of these contain intramolecular hydrogen bonds. The procedure for conformational analysis using the lanthanide ions [5] is very different in that it is essentially an absolute method. It is not based on combinations of two or three conformations derived from energy calculations nor is the search for single conformations weighted by published crystal structures. The results of our studies indicate that small peptides adopt a fairly extended conformation in aqueous solution, though they are not usually random coil configurations, and that the amino acid residue sidechains considerably affect the chain conformation. There is some dependence of the conformation upon the exact Ln(III) cation bound to the peptide. The influence of the structure of water on the conformation adopted by the peptide chain has also been observed.