Nonapeptides

A reevaluation of the original sequence data established that natural bradykinm was indeed the nonapeptide shown Here the synthesis of a peptide did more than confirm structure synthesis was instrumental m determining structure... 

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). 

Vasopressin and Oxytocin. Arginine -vasopressin (AVP, vasopressia also known as antidiuretic hormone, ADH) (342) is a nonapeptide amide that functions both as a neuroregulator and a hormone (84,85). Oxytocia (OT) (343) is a nonapeptide amide related to AVP. 

Clinical use of lL-1, lL-6, and TNF- a, is limited by associated systemic toxicity. SCF seems better tolerated. It may be possible to develop derivatives of other cytokiaes that are less toxic. The synthetic nonapeptide VQGEESNDK (position 163—171 of human lL-1 P) (see Amino acids ... 

Protein engineering) kicreases the survival of mice when kijected 20 h before or immediately after exposure to 8.5 Gy (850 rad) TBl (171). Although the nonapeptide is less effective than lL-1 P, it does not exhibit the IL-l-like inflammatory side effects of the whole molecule. 

Oxytocin [50-56-6] M 1007.2, m dec on heating, [a] -26.2"(c 0.53, N AcOH). A cyclic nonapeptide which was purified by countercurrent distribution between solvent and buffer. It is soluble in H2O, rt-BuOH and isoBuOH. [Bodanszky and du Vigneaud J Am Chem Soc 81 2504 1959 Cash et al. J Med Pharm Chem 5 413 1962 Sakakibara et al. Bull Chem Soc Jpn 38 120 1965 solid phase synthesis Bayer and... 

What is the amino acid sequence of this nonapeptide ... 

Leuprolide is a synthetic nonapeptide used to treat both endometriosis in women and prostate cancer in men. 

What is the structure of a nonapeptide that gives the following fragments when cleaved ... 

Oxytocin, a nonapeptide hormone secreted by the pituitary gland, functions by stimulating uterine contraction and lactation during childbirth. Its sequence was determined from the following evidence ... 

Bradykinin is a nonapeptide enzymatically produced from kallidin in the blood, where it is a potent agent of arteriolar dilation and increased capillary permeability. 

Peflin presents 40.9% identity with ALG-2. The protein has a long hydrophobic N-terminal extension containing nine nonapeptide repeats. Peflin is ubiquitously expressed. The function of peflin is still unknown, although recent experiments have shown a role in apoptosis. 

AVP and OT are cyclic nonapeptides with a disulphide bridge between the cysteine residues 1 and 6, resulting in a six-amino acid ring and a COOH-terminal a-amidated three-residue tail. OT differs only in two amino acids from AVP lie in position 3, which is essential for OT recqrtor (OTR) stimulation and Leu in position 8. AVP has a Phe in position 3 and an Arg in position 8. Arg 8 is essential for acting upon vasopressin receptors (Fig. 1). Lysipressin, found in pigs and some marsupials, has a Lys in position 8 [1]. 

XIa and also releases bradykinin (a nonapeptide with potent vasodilator action) from HMW kininogen. 

Proteins have been isolated from many cereal seeds that have extensive regions of repeating hexa- to nonapeptides. The consensus repeats are rich in Pro and Gin, and always contain an aromatic amino acid, generally Tyr. The CD spectra of fragments of these proteins containing the repeating sequence have been reported (DuPont etal., 2000 Gilbert... 

Schoenenberger, G. A., Maier, P. F., Tobler, J. H. Monnier, M. (1977). A naturally occurring delta-EEG enhancing nonapeptide in rabbits. X. Final isolation, characterization and activity test. Pflugers Arch. 369, 99-109. 

Opioid tetrapetide Opioid pentapeptide Octapetide Nonapeptide Tachykinin decapeptide Tachykinin undecapeptide Trisdecapeptide Opioid hexadecapeptide Opioid heptadecapeptide... 

Recently, Noort et al developed a procedure that is based on straightforward isolation of adducted BuChE from plasma by means of affinity chromatography with a procainamide column, followed by pepsin digestion and LC/electrospray tandem MS analysis of a specific nonapeptide containing the phosphonylated active site serine-198 residue (5). This method surpasses the limitations of the fluoride-reactivation method, since it can also deal with dealkylated ( aged ) phosphonylated BuChE. The method allowed the positive analysis of several serum samples of Japanese victims of the terrorist attack in the Tokyo subway in 1995. Furthermore, the method could be applied for detection of ChE modifications induced by, e.g., diethyl paraoxon and pyridostigmine bromide, illustrating the broad scope of this approach. This new approach... 

Blood Analysis of phospho-rvlated peptides Phosphyla-ted BuChE LC-MS-MS (after enzymatic digestion of modified cholinesterase. Phosphylated nonapeptides i.s. plasma exposed to CD3-OP Covers all OP s LOD 1-5% BuChE inhibition Expensive instrumentation and reference compounds... 

J Heibl et al. Large-scale synthesis of hematoregulatory nonapeptide SK F 1077647 by fragment coupling. J Pept Res 54, 54, 1999. 

From an entirely different source, namely, the venom of the snake Bothrops iararaca, scientists at Squibb isolated a nonapeptide (SQ 20,881, LXXI) which is a potent inhibitor of the converting enzyme (99). 

Comparison of SQ 20,881 with fifty-seven related synthetic peptides indicated that the last five amino acids of the sequence are required for significant enzyme inhibiting activity (100). This nonapeptide, intravenously, lowered blood pressure even in patients with normal renin levels (101. 102). This effect is strongly augmented by sodium depletion. 

Bradykinin (Fig. 6.34) is a vasoactive nonapeptide that is hydrolyzed by a variety of peptidases. Its N-terminus is susceptible to cleavage, but only by aminopeptidase P (X-Pro aminopeptidase, EC 3.4.11.9). Dipeptidyl-pepti-dase IV can then cleave the N-terminus dipeptide of bradykinin-(2-9). However, most cleavage reactions have been found to occur at or close to the C-terminus, with angiotensin-converting enzyme (ACE, peptidyl-dipeptidase A, EC 3.4.15.1) playing an important role. In fact, aminopeptidase P and ACE accounted for ca. 30 and 70%, respectively, of total bradykininase activity in the isolated perfused rat heart [164], As shown in Fig. 6.34, ACE... 

Further susceptibilities of the nonapeptide are shown in Fig. 6.34. Thus, the Pro7-Phe8 bond is also cleaved by neprilysin (EC 3.4.24.11) and endothelin-converting enzyme (EC 3.4.24.71) [149][165]. The C-terminal residue is susceptible to cleavage by several carboxypeptidases, particularly carboxypeptidase N. Thimet oligopeptidase (EC 3.4.24.15) is also able to act on bradykinin, which is cleaved at the Phe5-Ser6 bond [144],... 

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