Peptide Hormones in Medicine: A 100-Year History

Abstract

This review is devoted to the 100-year history of the investigation of peptide hormones and the creation of drugs on their basis, starting from the insulin discovery and its introduction into a medical practice in 1921. The basic groups of the peptide hormones are discussed: neurohypophyseal hormones, hypothalamic releasing hormones, incretins, insulin, adrenocorticotropic hormone (ACTH), and calcitonin. The first therapeutic agents based on the peptide hormones were created by a traditional approach that involved the isolation of peptides from animal tissues, their purification to individual compounds, determination of their primary structure, their chemical synthesis or their deep purification, and the creation of a pharmaceutical substance. A modern approach to creation of peptide hormone drugs is based on their consideration as ligands of the corresponding cellular receptors and the use of computer modeling, efficient synthesis methods, and high-throughput screening. The combination of these methods enabled the development of analogs which would be more active than the corresponding natural compounds, exhibit other activities in addition to the hormonal regulation, and be resistant to biodegradation. Such therapeutic agents have been designed on the basis of agonistic and antagonistic analogs of somatostatin and luliberin, and have found wide application in hormonal regulation and cancer treatment. Over the past two decades, the glucagon-like peptide (GLP-1) has been intensively investigated as a potential therapeutic agent. In our review, we describe modifications which resulted in the most highly effective long-acting drugs. Now, natural hormones and their analogs are widely present in the pharmaceutical market.

Cyclic Peptides for Drug Development

“…For example in medical conditions in which the body does not produce sufficient hormone, supplementing with the affected hormone can restore balance and alleviate associated symptoms. [12] The first cyclic peptide hormones exploited as drugs were oxytocin and vasopressin, introduced to the clinic in 1960s. Initially identified and synthesized in the 1950s by du Vigneaud, both hormones are nonapeptides that feature a six-amino-acid ring closed by a disulfide bridge.…”

“…Several human hormones are based on cyclic peptides, and synthetic versions of them can thus be used to regulate various body processes and functions. For example in medical conditions in which the body does not produce sufficient hormone, supplementing with the affected hormone can restore balance and alleviate associated symptoms [12] . The first cyclic peptide hormones exploited as drugs were oxytocin and vasopressin, introduced to the clinic in 1960s.…”

Protein Drugs

“…Trước đó, hormone peptide thường được sử dụng cho liệu pháp thay thế nội tiết tố để khôi phục trong trường hợp cơ thể giảm hoặc ngừng tiết. Ngày nay, phạm vi ứng dụng rộng hơn nhiều [9,13]. Một số thuốc hormone peptide được trình bày trên Bảng 4.…”

Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications

“…Several naturally occurring peptides present, alone, important biological fun being fully functional entities [39]. Relevant examples of peptides and small prote the vertebrate hormones, insulin (51 residues), glucagon (29 residues), and cortic (39 residues), and many drugs have been developed on their basis, including by u amino acids and other residue modifications [42]. Other examples of small natur curring peptides are the endogenous hormones oxytocin [43] and thyrotropin [44] Importantly, although by definition there are 20 L-amino acids encoded by the genetic code, there are two other residues that are proteinogenic: selenocysteine (Sec) and pyrrolysine (Pyl) (Figure 1G,H) [33,34].…”