A-Endorphin

Ling N. Solid-phase synthesis of porcine a-endorphin and y-endorphin, two hypothalamic-pituitary peptides with opiate activity. Biochem. Biophys. Res. Commun. 1977 74 248-255. 

Endorphins. The endorphins have been defined as a class of opioidacting peptides isolated from brain, all of which seem to be fragments of 3-iipotropin.22 39 The endorphins have the following structures a-Endorphin (3-lipotropin l-7 )... 

L6. Ling, N., Burgus, R., and Cuillemin, R., Isolation, primary structure and synthesis of a-endorphin and 7-endorphin, two peptides of hypothalamic-hypophysial origin with morphinomimetic activity. Proc. Natl. Acad. Sci. U.S.A. 73, 3942-3946 (1976). 

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]. 

This sensitivity is superior to that attained by other methods. Postcolumn reaction with o-phthalaldehyde has been used to detect the tryptic peptides generated from several hundred picomoles (10 jig) of human globulin (Benson, 1976). Generally, about 1 /xg of a protein is required for visualizing a band on a polyacrylamide gel by staining with Coomassie blue. Ultraviolet absorption at 210 nm was used by Ling et al. (1976) to monitor the chromatographic purification of about 200 nmol of a-endorphin. 

Figure 10. Chromatography of a-endorphin (A) and y-endorphin (B) on Lichro-sorb RP-18. The latter peptide has, in addition to the same sequence of 16 amino acides found in the former, a leucine residue at the COOH-terminal.

Figure 6 The fragmentation of a-endorphin protonated molecule after FAB ionization (1984 example provided by M-Scan Ltd.).

NHR STUDIES ON OPIOID PEPTIDES C-ENRICHED METHIONINE-ENKEPHALIN AND a-ENDORPHIN... 

TABLE 1. Chenlcal shifts of a-endorphin and ethlonine-enkephalln In D2O. ... 

Fig. 11. Fast atom bombardment mass spectrum of a-endorphin showing both molecular weight and sequence ion information.

Four groups of endorphins have been identified a-endorphin contains 16 amino acids, /3-endorphin contains 31 amino acids, y-endor-phin has 17 amino acids, and S-endorphin has 27 amino acids. Endorphins may produce their sedating effects by preventing the release of substance P, a polypeptide with 11 amino acids, which has been found to transmit pain impulses to the brain. 

Fig. 1.8. The organization of a multicomponent precursor synthesized in the pituitary and yielding by cleavage different hormones (according to Tata, 1978 Roberts and Herbert, 1977a,b Roberts et al, 1978). This precursor molecule has a molecular weight of 31,000 and is composed of about 260 amino acids. The hormone ACTH has 39 amino adds and is released by proteolytic cleavage of the N-terminal end further cleavage of ACTH gives peptide 1-13 which is a-MSH. jS-Lipotropin is formed by 91 amino adds in C-terminal position it contains jJ-MSH, endorphins and enkephalins which are also obtained by proteolytic cleavage. Peptide 61-76 is the a-endorphin 61-77 the y-endorphin 61-91 which represents the C-terminal fragment is the / -endorphin and 61-65 is the Met-enkephalin (from Tata, 1978).

---