TABLE OF CONTENTS The coverage in this Chapter reflects the recent interest in these molecules, as (i) structures evolved by Nature which have been useful templates of biological activity, as either antibiotics or cytotoxic peptides, or (ii) the development of cyclic peptide analogues of naturally-occurring peptides as a means of introducing conformational constraints, to improve receptor interaction and reduce the biodegradability of peptides by enzymes. The latter approach represent key steps in the pharmaceutical industry's quest for peptidomimetic structures for drug development. The nomenclature used in the discussion will rely heavily on the three-letter amino-acid notation and IUPAC Rules [1], with the terms, cyclic homodetic peptides representing peptides where all the cyclic backbones comprise peptide bonds, while cyclic heterodetic peptides refer to cyclic backbones bearing other functional groups, e.g. ester bonds or Nature's own cyclic constraint, the disulfide link. Comprehensive coverage of the topics highlighted can be obtained from review articles produced annually [2], or as expert updates of specific areas [3].
Whether it be for proof of structure, or for studying the conformation of the constrained cyclic peptides, most of the modern physical methods have been applied to this field. Structural elucidation is now often all-encompassing, in that high-field nmr techniques, X-ray studies and other methods appear in one publication. Some of the very early applications of X-ray crystallography were on the cyclodepsipeptide family related to valinomycin. Recent investigations [4] of new crystalline forms within this family, reflect...
