Synthetic peptides oxytocin

Impaired milk ejection may respond to nasal oxytocin. Synthetic peptide and nonpeptide oxytocin antagonists that can prevent premature labor are being investigated. 

Oxytocin, desmopressin, cer-betocin and related synthetic peptides CEC Hypersil C8, CEC Hypersil Cl8, 5 pm, Spherisorb mixed mode C18/SCX phase 3 pm Triethylamine buffers, pH 3.0 adjusted with phosphoric acid with different proportion of acetonitrile 335 mm x 100 pm i.d. 250 mm packed length... 

Synthetic peptides such as oxytocin, vasopressin, ACTH, calcitonin, secretin, somatostatin, cyclosporine, and insulin are already in clinical use. 

A number of synthetic peptides are significant commercial products, ranging from the sweet dipeptide aspartame (L-aspartyl-L-phenylalanine methyl ester) to clinically used hormones such as insulin and oxytocin. L-Aspartyl-L-phenylalanine methyl ester (3 Scheme 2) is the methyl ester of the C-terminal dipeptide of gastrin. It was found accidently during the synthesis of gastrin that this synthetic sweetener is about 200 times as sweet as sucrose.f This pleasant sweetness without a bitter aftertaste was the reason that L-aspartyl-L-phenylalanine methyl ester was approved in many countries as a food additive, receiving much attention as a low-calorie sweetener. L-Aspartyl-L-phenylalanine methyl ester can be prepared by various chemical routes and the first enzymatic procedure of commercial interest was described by Isowa et al.h l In the industrial process,L-Asp and DL-Phe were chosen as inexpensive raw materials. L-Asp is available very inexpensively, whereas L-Phe is more expensive than DL-Phe. Z-D-Asp acts as a competitive inhibitor, while D-Phe-OMe... 

Synthetic peptides are gaining importance as newer synthetic methods are being developed one may mention bradyldnin and analogues [134—136], oxytocin analogues [137], polymyxin [138, 139] and corticotropically active polypeptides [139a]. 

The subject 0xytocin - molecular aspects can be treated from various points of view. One of the possible approaches is the following To-day we have quantitative data on a nximber of well-defined pharmacological properties for more than 200 synthetic peptides of the nexirohypophysial type, which can all be considered to be derivatives of oxytocin. Therefore, it is tempting to try to discover, on the basis of the pharmacological properties of these derivatives, which parts of the oxytocin molecule are essential for the characteristic biological effects of this hormone. 

This introduction would not be complete without mentioning a few key events in the history of peptide synthesis. In 1901 Emil Fischer reported the synthesis of a peptide, Leonidas Zervas developed the Z (Cbz) protecting group in 1932, and Vincent du Vigneaud was awarded the Nobel Prize in 1955 for the chemical synthesis of the cyclic peptide, oxytocin. In 1963 Robert Bruce Merrifield introduced the concept and the first implementation of solid-phase peptide synthesis for which he was awarded the 1984 Nobel Prize in chemistry [1,2]. Solid-phase peptide synthesis has for decades been the primary source of synthetic peptides on a laboratory scale. 

C Johansson, L Blomberg, W Hlebowicz, H Nicklasson, B Nilsson, L Andersson. Industrial production of an oxytocin antagonist Synthetic approaches to the development of a multi-kilogram scale solution synthesis. (Atosiban) In HLS Maia, ed. Peptides 1994. Proceedings of the 23rd European Peptide Symposium. Escom, Leiden, 1995, pp 34-35. 

The iodine oxidation method has also been applied in one-pot synthetic strategies to mono-disulfide peptides in which the bis-cysteine peptide is cleaved from the resin, depro-tected, and oxidized in a single step.163 64 A comparative analysis of the iodine procedure (TFA/10 equiv I2) with other TFA/oxidant mixtures using oxytocin as the target model peptide clearly revealed formation of side products to a significant extent. 85 ... 

The methods presented in the sections above are all suitable for the synthesis of lanthionines as amino acid derivatives. However, a very important synthetic goal remains the synthesis of lanthionine-containing peptides, for example the synthesis of lantibiotics and other peptide analogues where lanthionine has replaced cystine. In the following Sections some syntheses of lanthionine-containing peptides comprising analogues of cystine peptides, such as enkephalin, somatostatin, and oxytocin are described. 

Historically, the first important cysteine protecting group was the 5-benzyl group, developed by du Vigneaud etal. and used in the classical synthesis of oxytocin,t as well as in the syntheses of a number of cysteine-containing peptides in the first years of solid-phase synthetic methodology.P l This 5-Bzl protection is nowadays used infrequently due to the fact that its removal involves harsh conditions, e.g. sodium in liquid ammoniat or anhydrous hydrogen fluoride at 20°C,t conditions which may lead to side reactions such as elimination... 

Oxytocin is a hormone involved in controlling the onset of labour in women and the subsequent release of milk. It was the first peptide hormone to be synthesized, in 1953, and the synthetic version of the hormone, Syntooinon (identical, of course, with the natural version isolated... 

Advantages of the solid-phase method are amenability to automation, the almost 100% yield of product for each reaction, the ease of removal of excess reagents and waste products by washing and filtration of resin particles, the lack of need for purification of intermediates, and speed. Peptides or proteins that have been synthesized by the solid-phase method include ribonuclease, bradykinin, oxytocin, vasopressin, somatostatin, insulin, and the S-chain of hemoglobin. The sequence analyses for these substances were confirmed by demonstrating that the synthetic products, constructed on the basis of sequence data, had the same biological activities as those of the corresponding natural substances. 

A rational total synthesis is used for some simple alkaloids (adrenaline, theophylline, papaverine), low molecnlar peptide hormones (oxytocin, vasopressin), vitamins (biotin, folk acid, thiamine, riboflavin), phenolic acids (sahcyhc acid). It should, however, be observed that the synthetic substances are all racemic forms, whereas many natural products occur in the 1-form. 

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