Oxytocin analogs

Oxytocin Neurohypophysis planar by layer. Inhibits carbon dioxide synthesis. Oxytocin analog antagonizes oxytocin... 

Even this brief discussion of oxytocin analogs can not be concluded without pointing out that Nature experimented with hormone analogs well before organic chemists undertook the synthesis of such compounds. Thus, 8-isoleucine oxytocin (mesotocin) was discovered in the frog [56], 4 serine-8-isoleucine oxytocin (isotocin) in teleost fishes [57] and 4-serine-8-glutamine oxytocin (glumitocin) in the ray [58]. 

Table 3. Conformational restrictions and structural features apparently related to antagonist activity in oxytocin analogs... 

A number of oxytocin analogs have been prepared using the S-benzyl group a summary may be found in the volumes by E. Schroder and K. Liibke, The Peptides , Academic Press, New York, N.Y. 1965. 

Oxytocin, a nine amino acid peptide, is synthesized primarily in the paraventricular and supraoptic (SON) nuclei of the hypothalamus, from which it is released to the general circulation through the posterior pituitary (Insel et ah, 1997). However, oxytocinergic fibers have also been found to project from the PVN to the limbic system and several autonomic centers in the brain stem. This central OT pool appears to be independent of pituitary OT release cerebrospinal fluid (CSF) and plasma OT responses to numerous stimuli are not correlated (Insel, 1997). Oxytocin and its analog (or partner) peptide vasopressin are found only in mammals. A related peptide, vasotocin, thought to be the evolutionary precedent of these peptides, is found in reptiles and birds. The first known actions of OT were its peripheral effects on the physiology of new mothers. In mammals, OT stimulates milk ejection and uterine contraction, essential aspects of maternal physiology (Insel et ah, 1997). 

A number of excellent publications have now appeared dealing with NMR studies of oxytocin (14,15), vasopressin (16,17), and their analogs. These follow the earlier pattern set in the gramicidin SA study and are of great value in forming ground rules for interpretation of NMR data. 

These peptide hormones are among the best-researched active peptide substances. More than 350 oxytocin and vasopressin analogs have been reported in the literature. 

Replacement of Pro5 by its sulfur analog, thiazolidine-4-carboxylate (Thz), a strategy that led to enhanced activities in oxytocin derivatives, yielded the potent peptide [D-Met2, Thz5]-enkephalinamide, 4 to 5 times as potent as morphine (MTF, iv)/91 ... 

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