BRAIN OLIGOPEPTIDES

The synthesis of peptide antagonists has greatiy aided in the development of knowledge of other neuropeptide systems as well. 

Many neurotransmitters are remarkably potent, both in vivo as well as in binding to their respective receptors. Many peptides exhibit dissociation 

Synthesis. In contrast to pituitary hormones, which usually can be obtained in pure form only after extraction from animal tissues, brain oligopeptides are readily available because of their small size. The synthetic repHca represents the most economical and readily accessible source for the oligopeptides. Two techniques are available for laboratory synthesis of oligopeptides, ie, solution chemistry and soHd-phase peptide synthesis (SPPS). 

These methodologies have been reviewed (22). In both methods, synthesis involves assembly of protected peptide chains, deprotection, purification, and characterization. However, the soHd-phase method, pioneered by Merrifield, dominates the field of peptide chemistry (23). In SPPS, the C-terminal amino acid of the desired peptide is attached to a polymeric soHd support. The addition of amino acids (qv) requires a number of relatively simple steps that are easily automated. Therefore, SPPS contains a number of advantages compared to the solution approach, including fewer solubiUty problems, use of less specialized chemistry, potential for automation, and requirement of relatively less skilled operators (22). Additionally, intermediates are not isolated and purified, and therefore the steps can be carried out more rapidly. Moreover, the SPPS method has been shown to proceed without racemization, whereas in fragment synthesis there is always a potential for racemization. Solution synthesis provides peptides of relatively higher purity however, the addition of hplc methodologies allows for pure peptide products from SPPS as well. 

The use of SPPS allows synthesis of both native oligopeptides and important synthetic analogues. Many of these fragments or substituted analogues have been found to be equal to, or more potent than, the parent molecule and to exhibit long-acting and antagonistic activities. 

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The principal hormones of the human posterior pituitary include the two nonapeptides, oxytocin [50-56-6] and arginine vasopressin [11000-17-2] (antidiuretic hormone, ADH). Many other hormones, including opioid peptides (see Opioids, endogenous), cholecystokinin [9011-97-6] (CCK) (see Hormones, BRAIN oligopeptides), and gastrointestinal peptides, also have been located in mammalian neurohypophysis (6), but are usually found in much lower concentrations (7). Studies have demonstrated that oxytocin and vasopressin are synthesized in other human organs, both centrally and peripherally, and there is considerable evidence for their role as neurotransmitters (see Neuroregulators) (8). 

Fig. 1. Schematic drawing of precursors for selected brain oligopeptides. Shaded areas represent the location of sequences of active peptide products which are normally cleaved by trypsin-like enzymes acting on double-basic amino acid residues. Precursors are not necessarily drawn to scale, (a) CRF precursor (b) proopiomelanocortin (POMC) (c) P-protachykinin (d) proenkephalin A (e) CGRP precursor (f) preprodynorphin, ie, preproenkephalin B. Terms are...

Table 1. Names and Properties of Selected Brain Oligopeptides...

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