60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective

Abstract

Many important fields of research had a humble origin. In the distant past, A J P Martin's discovery that amino acids could be separated by paper chromatography and Moore and Stein's use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world's great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of β-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain.

Transgenic increase in the β‐endorphin concentration in cerebrospinal fluid alleviates morphine‐primed relapse behavior through the μ opioid receptor in rats

“…A previous observational study investigated the decrease in β‐EP in opioid addiction models, especially in the blood, spinal cord, and brain nuclei . Our previous work and that of others confirmed that upregulation of exogenous β‐EP could attenuate withdrawal syndrome in opioid‐dependent rats . Moreover, studies have shown that glycyl‐glutamine, DTgammaE, and DEgammaE, which are the active peptide and fragments derived from β‐EP, respectively, present favorable effects on attenuation of opioid withdrawal symptoms .…”

“…12,13 Our previous work and that of others confirmed that upregulation of exogenous β-EP could attenuate withdrawal syndrome in opioiddependent rats. [14][15][16][17] Moreover, studies have shown that glycylglutamine, DTgammaE, and DEgammaE, which are the active peptide and fragments derived from β-EP, respectively, present favorable effects on attenuation of opioid withdrawal symptoms. 11,18 This evidence strongly indicates that β-EP plays an important role in preventing opioid addiction.…”

POMC: The Physiological Power of Hormone Processing

“…This has been attributed to its sequence, which confers resistance to degradation. There is also the suggestion that the more COOH-terminal region of ␤-endorphin acts in "an address function," by presenting the peptide to the receptor to aid specificity and potency (378). This could be considered another advantage of the presence of a peptide within a larger pro-hormone structure.…”

60 YEARS OF POMC: Purification and biological characterisation of melanotrophins and corticotrophins

“…An equivalent peptide had not been identified in extracts of murine pituitary glands, but a β-MSH-like peptide with a four-amino acid N-terminal extension (Ala-Glu-Lys-Lys) had been isolated from human pituitaries extracted at mild pH (Dixon 1960). In those mammals in which the primary structure of β-lipotrophin (β-LPH) was elucidated, it was revealed that they all contained the sequence of their appropriate β-MSHs (banded by double basic amino acids: Lys-Arg or Arg-Arg), and thus, it was naturally assumed that β-LPH could be the precursor of β-MSH by simple proteolytic processing at the double basic residues by trypsin-like activity (Chretien & Mbikay 2016, Smyth 2016. The situation with human β-MSH was atypical, as it appeared not to be cleaved from its β-LPH at the N-terminal Lys-Lys double basic motif but in a non-trypsin-like manner at an Ala-Ala peptide bond.…”