Diffraction Studies of Model and Natural Helical Peptides

Abstract

The discovery of naturally occurring peptides that form voltage-gated ion channels in bilayer membranes has provided an impetus for the study of structural characteristics of this class of peptides (Mueller and Rudin, 1968; Mathew and Balaram, 1983). The relative difficulty of obtaining crystals of the natural peptides and determining their structure has led to the synthesis of many apolar peptides that are fragments or analogs of the natural peptides. The naturally occurring peptides contain a number of a-aminoisobutyric acid (Aib) residues, (Fig. 16.1) which have proven to be strong helix formers (Marshall and Bosshard, 1972; Burgess and Leach, 1973; Balaram, 1984). A review of crystal structures of small linear peptides, containing up to five residues including at least one Aib residue, demonstrated that 28 out of 29 structures have an incipient 310-helix (Toniolo et al., 1983). Thirty-three crystal structures of 7–16 residue apolar peptides containing one or more Aib residues have shown completely helical conformations with a 310-helix, an α-helix, or a mixed 310/ α-helix, depending mostly upon the length of the peptide and the number of Aib residues (Karle and Balaram, 1990).