Peptides

Abstract

AbstractPeptide antibiotics are classified according to their overall shape, which can be linear or cyclic, and by the nature of the bonds joining the constituent amino acids and other carboxylic acids, which can be all amide bonds or amide plus ester bonds. Most peptide antibiotics are cyclic peptides that do not contain disulfide linkages. Peptide antibiotics differ in many respects from proteins. The vast majority of peptide antibiotics have molecular weights in the 500–1500 range, whereas the average protein has a mol wt of 40,000. Many peptide antibiotics have unusual fatty acids and amino acids, such asD‐amino acids,N‐methyl amino acids, or imino acids, and they usually lack methionine and histidine. Ring closure in cyclic peptide antibiotics is by amide or ester bonds. Peptide antibiotics are normally resistant to the usual proteases and peptidases. They are usually synthesized on multienzyme complexes much as are fatty acids, and not on ribosomes as are proteins. Most peptide antibiotics are synthesized as groups of closely related structures. Even the small fraction of peptide antibiotics that have therapeutic usefulness are quite toxic. The ratio of the minimum toxic dose to the maximum effective dose is smaller than for most nonpeptide antibiotics. Peptide antibiotics are not often the drugs of first choice for systemic therapy of important human disease. However, the World Health Organization, which chooses drugs especially for Third World use based on efficacy, safety, quality, price, and availability, includes such peptide antibiotics as bleomycin, dactinomycin, and bacitracin, plus several β‐lactams. The complex structure of peptide antibiotics adds considerably to the problems of synthesis, but more recent efforts toward improved peptide antibiotics are encouraging.