Hydrogen bonds in molecular assemblies of natural, synthetic and ‘designer’ peptides

Abstract

The initial folding of the backbone of peptides and the subsequent arrangement of the molecules into a supramolecular assembly is primarily associated with NH⋯OC hydrogen bonds where the N⋯O distance is 2.8–3.0 Å and to a lesser extent with water molecules that act as donors and acceptors for hydrogen bonds, both within a peptide molecule and between peptide molecules. In helical peptides, the transition between 3 10-helices (with 10 atoms in a hydrogen-bond ring) and α-helices (with 13 atoms in a hydrogen bond ring) merely requires a shift from one CO to an adjacent CO and is often quite facile. Among examples to be presented are two crystal structures of a heptapeptide wherein the helices are the 3 10-type when the amino end group is Boc and the α-type when the amino end is Ac. A new type of regular helix was synthesized and characterized by x-ray diffraction analysis using β-amino acid residues, rather than α-amino acid residues. The new helix was named β-foldamer and it is characterized by 14-atom hydrogen-bond rings rather than the 13-atom rings present in α-helices. An NH group will not always form a hydrogen bond with any CO (or H 2O) that is present in a crystal. Examples are shown in which the N⋯O distance is > 3.30 A ̊ and also examples of structures in which there is no O acceptor or any other kind of acceptor within possible reach of an available NH. Assemblies with ‘free’ NH groups are presented in which there is no possibility for a ‘cooperative hydrogen bond’ between NH and the center of a phenyl group, although other structures with a close NH⋯phenyl approach will be discussed.