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This special issue reviews applications of various types of molecular constraint to bioactive molecules, especially those with therapeutic potential. Constraints are used not only for improving their pharmacological profiles, including activities and receptor specificities, of existing bioactive peptides but also to provide information on the way in which these peptides bind to their receptor and thus aid in the development of non-peptide, orally-deliverable pharmaceuticals. Leading off, Lowell et al overview the application of conformational constraints as a strategy for improved drug design and this provides a background for the more specialized reviews that follow. Backbone methylation of peptide hormones has proven to be a powerful method for changing their receptor specificity and Sagan et al review these effects and the chemistry of synthesizing backbone-methylated peptide analogues. Reissmann and Imhof describe the application of constrained amino ands and different cyclization techniques to the development of conformationally restricted bradykinin and somatostatin analogues. Calcitonin and parathyroid hormone are two peptide hormones currently used in the treatment of bone diseases, particularly osteoporosis. Kapurniotu reviews the use of conformational constraints for understanding the structural and conformational requirements for calcitonin bioactivity and for deriving more powerful agonists. Finally, Willick et al review the application of cyclization to understanding the receptor action of parathyroid hormone, parathyroid hormone-related peptide, and the osteogenic growth peptide and the development of analogues with improved activities and specificities. These reviews should be useful not only to workers with the peptides described here, but also to those working with others of the many important bioactive peptides. Such work promises to be a rich source of therapeutics for the future.
Institute for Biological Sciences National Research Council Ottawa, ON Canada, K1A 0R6.
Publication date: November 1, 2004
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Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.