Identification of two related pentapeptides from the brain with potent opiate agonist activity

@article{Hughes1975IdentificationOT,
  title={Identification of two related pentapeptides from the brain with potent opiate agonist activity},
  author={John Hughes and T. W. Smith and Hans Walter Kosterlitz and Linda A. Fothergill and Barry A. Morgan and Howard R. Morris},
  journal={Nature},
  year={1975},
  volume={258},
  pages={577-579}
}
Enkephalin, a natural ligand for opiate receptors is composed of the pentapeptides H–Tyr–Gly–Gly–Phe–Met–OH and H–Tyr–Gly–Gly–Phe–Leu–OH. The evidence is based on the determination of the amino acid sequence of natural enkephalin by the dansyl–Edman procedure and by mass spectrometry followed by synthesis and comparison of the natural and synthetic peptides. 

Opiate receptor affinity of peptides related to Leu-enkephalin.

Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates

Hughes et al.5 have shown that the opiate activity isolated by them is due to a mixture of two peptides H–Tyr–Gly– Gly–Phe–Met–OH and H-Tyr-Gly-Phe-Leu–OH termed methionine-enkephalin and leucine- enkephaline respectively.

Potent tetrapeptide enkephalins.

Evidence for analgesic activity of enkephalin in the mouse

It is indicated that the two natural compounds induce analgesia in mice, whereas the two analogues are devoid of such activity.

Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor.

  • R. SimantovS. Snyder
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1976
Sodium and manganese effects on opiate receptor interactions show that both peptides are agonists, whereas leucine enkephalin may be a "purer" agonist than methionine enkphalin.

Analogues of both Leu- and Met-enkephalin containing a constrained dipeptide isostere prepared from a Baylis-Hillman adduct

An efficient route was developed for the synthesis of the Fmoc-protected dipeptide 4, isostere of Gly-Gly containing an α-methylene β-amino acid; the conformationally restricted analogues of
...

References

SHOWING 1-10 OF 16 REFERENCES

Search for an endogenous ligand for the opiate receptor.

The factor inhibited binding to the opiate receptor in synaptic plasma membranes of rat brain and to the receptor of the guinea-pig ileum although it was less effective on the latter, particularly after long-term incubation.

Isolation and Amino-acid Sequence of β-LPH from Sheep Pituitary Glands

In the course of investigating a simplified procedure for the isolation of ACTH from sheep pituitary glands, a lipotropic peptide is obtained which is chemically distinct from ACTH and other known adenohypophyseal hormones.

A mass-spectrometric sequence study of the enzyme ribitol dehydrogenase from Klebsiella aerogenes.

The first detailed results of the application of a low-resolution mixture analysis approach to the sequence analysis of an enzyme, ribitol dehydrogenase, are given and the overall sequencing strategy evolved is assessed.