Pro-dynorphin

The Group III peptides come from the 256-amino acid precursor, pro-dynorphin [88402-55-5] (pro-enkephalin B). This group contains dynorphin A [80448-90-4] and B [85006-82-2] as weU as a-neoendorphin [77739-20-9] (Fig. 2), all of which can be further cleaved to form biologically active iatermediates, eg, dynorphin A g and P-neoendorphin [77739-21-0] (a-neoendorphin ) (28). The longer of these peptides are relatively basic because of the number of Lys and Arg residues. 

A2 23, and D-Pro -dynorphin A 23 (97). Analogues with C-terminal deletions, such as D-Pro -dynorphin have been found to display further... 

The classic endogenous opioid peptides are derived from one of three families of precursors proopiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. Many active opioid peptides are derived from these three, but the best known are )S-endorphin, enkephalin, and dynorphin. POMC is produced by nuclei in the hypothalamus and medulla (Khachaturian et al. 1985 Watson et al. 1978 Bloom et al. 1978). Enkephalin and dynorphin neurons are distributed to all levels of the central nervous system (Hokfelt et al. 1977 Khachaturian et al. 1983 Sar et al. 1978 Khachaturian et al. 1985). 

Precursor peptides (1)pro-endomorphin (2)pro-opiomelanocortin, <3)pro-enkephalin, (4)pro-dynorphin, (5)pro-nociceptin ( presumed to exist). 

Dores, R. M., and Akil, H. (1985). Steady state levels of pro-dynorphin-related end products in the striatum and substantia nigra of the adult rhesus monkey. Peptides 6(Suppl. 2), 143-148. 

Pro ] dynorphin A-d-lDNHa was also reported to be a highly selective, but relatively weak, K-receptor antagonist (see Table 7.17) (781). 

Neoendorphins, opioid peptides derived from the precursor protein pro-dynorphin (pro-enkephalin B). a-Neoendorphin, H-Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys -OH, corresponds to the partial sequence of human and porcine pro-dynorphin-(175-184), and contains the sequence of -neoendorphin ([desLys ]-a-endorphin). Both neoendorphins show potent activity in the guinea pig ileum assay [K. Kangawa et al., Biochem. Biophys. Res. Commun. 1981, 99, 871 N. Minamino et al., Biochem. Biophys. Res. Commun. 1981, 99, 864]. 

An eloquent example of the biochemical complexity of peptide degradation in blood is afforded by dynorphin A-( 1-13) (Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys), a potent opioid peptide. When incubated at 37° with human plasma, dynorphin A-(l -13) had a tm value of < 1 min, and... 

Both Met-enkephalin and Leu-enkephalin have their own pro- and prepro forms.29 Bovine preproenkephalin A is a 268-residue protein containing a 20-residue signal sequence and four sequences of Met-enkephalin and one of Leu-enkephalin, each flanked by pairs of basic residues. There are also Met-enkephalin-Arg-Gly-Leu (YGGFMRGL) and Met-enkephalin-Arg-Phe sequences. Not all of these are cut out cleanly, and other peptides such as Met-enkephalin-Arg-Arg-Val-NH2 are also found in brain. Proenkephalin B contains three copies of Leu-enkephalin contained within longer peptides. One of these, P-dynorphin (Table 30-4), is also a potent opioid compound. The enkephalins are thought to act as neurotransmitters, which are rapidly degraded after their release by two or three membrane-bound... 

Penicillolysin showed a high affinity toward the Pro-X ( = Gin, Lys, Leu or Arg) bonds of substance P, dynorphin A [1-13], neurotensin and chicken brain pentapeptide, and the R-R bonds in dynorphin A and neurotensin (Figure 13) [69], Preferential cleavages of bonds by the enzyme with hydrophobic amino acid residues at the Pi position were observed on the peptides used (Figure 13). The specificity of penicillolysin differs from that of other metalloprotinases. 

Shukla VK, Bansinath M, Dumont M, Lemaire S (1992) Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(l-13)-Tyr-Leu-Phe-Asn-Gly-Pro. Brain Res 591 176-180... 

Three separate categories of endogenous substances with morphine-like activity have been identified. These families of neuropeptides are known as enkephalins, endorphins, and dynorphins. Each family is derived from a distinct precursor polypeptide (pro-enkephalin, pro-opiomelanocortin, and prodynorfin) and has a characteristic anatomical distribution. The enkephalins and dynorphins found co-exist with other neurotransmitters, such as serotonin (5-HT) and noradrenaline, but details of how the peptides modulate the activity of co-transmitters await elucidation. 

The possible conformations of dynorphin A have been studied by a variety of spectral techniques (see Ref 753 for a review). Like other linear peptides, a variety of conformations have been observed for dynorphin A, which depend on the experimental conditions. Schwyzer (755) proposed a membrane-assisted model for dynorphin s interaction with k receptors, in which theN-terminal "message" sequence adopts an a-helical structure from residues 1-9 when it binds to the receptor. NMR studies of dynorphin A bound to dode-cylphosphocholine micelles (756, 757) observed a helical structure in the N-terminal portion of the peptide, supporting this pro-... 

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