Biosynthetic origin and receptor conformation of methionine enkephalin

Bradbury, A. F.; Smyth, Derek G.; Snell, C. R.

doi:10.1038/260165a0

Cited by 175 publications

(57 citation statements)

References 9 publications

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“…In pig brain, methionineenkephalin is the preponderant species, but the reverse is true in bovine brain (Simantov & Snyder, 1976). The verification with purified preparations, that the peptides interact at the opiate receptor, combined with our own observations and those of other workers (Bradbury, Smyth & Snell, 1976) showing that conformations are possible for the peptide which could be said to resemble the structures of opiates, makes a more detailed conformational study of the enkephalins of particular interest.…”

Section: Introductionmentioning

confidence: 80%

A Conformational Analysis for Leucine‐enkephalin Using Activity and Binding Data of Synthetic Analogues

Beddell

Clark

Lowe

et al. 1977

British J Pharmacology

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Leucine‐enkephalin and some analogues were assayed for activity in vitro on the mouse vas deferens and for binding to opiate receptors from rat brain. The experimental data were analysed in terms of the stringency for glycine, a D‐amino acid or an L‐amino acid at each position in the peptide. The observed configurational specificity was compared with the stringency that would be predicted to occur if enkephalin adopted certain hydrogen‐bonded conformations at the receptor. A small subset of the conformations examined was found to be compatible with the experimental data.

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Section: Introductionmentioning

confidence: 80%

A Conformational Analysis for Leucine‐enkephalin Using Activity and Binding Data of Synthetic Analogues

Beddell

Clark

Lowe

et al. 1977

British J Pharmacology

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“…We constructed models of these molecules, and it was interesting to see that morphine which has a rigid molecular structure imposed by fused rings was very similar to the N-terminal region of β-endorphin when the peptide chain was folded in the β-turn predicted from its sequence (Bradbury et al 1976d). There was an even closer similarity with benzyloripavine, a potent synthetic derivative of morphine (Fig.…”

Section: Processing Of β-Endorphin and Melanotropin: Sensitivity To Pmentioning

confidence: 97%

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

Smyth

2016

Journal of Molecular Endocrinology

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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.

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“…Many conformational studies have been published using nmr (2, 3), fluorescence (4), theoretical studies (5)(6)(7), and more recently X-ray studies (8). Some of the conformations proposed can be correlated with synthetic opiates (9,10). However, among the many published studies which derived "active conformations" for the enkephalins there has been no real consensus.…”

Section: Introductionmentioning

confidence: 99%

The design and synthesis of nonpeptide compounds as mimics of a conformation of methionine-enkephaline

Bélanger¹,

Dufresne²,

Scheigetz³

et al. 1982

Can. J. Chem.

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A model for the active conformation of methionine-enkephalin containing a P-turn was derived from computer modeling. Using a trans-perhydronaphthalene as a structural template and a mimic of the p-turn, target compounds were designed and synthesized. Thus, a key intermediate, trans-3-oxo-5~-formamidomethyl-8a-phenylmethylperhydronaphthalene, was prepared by two different routes from cyclohexanone.The addition of a methionine-like side-chain to this key intermediate was best achieved by a reaction with the anion of methyl 2-trimethylsilyl-4-methylthiobutanoate. This led to the preparation of an exo-tetrasubstituted double bond in high yield. Subsequent addition of tyrosine through coupling with the 5P-aminomethyl group provided the desired perhydronaphthalene mimics of met-enkaphalin.

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Biosynthetic origin and receptor conformation of methionine enkephalin

Cited by 175 publications

References 9 publications

A Conformational Analysis for Leucine‐enkephalin Using Activity and Binding Data of Synthetic Analogues

A Conformational Analysis for Leucine‐enkephalin Using Activity and Binding Data of Synthetic Analogues

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

The design and synthesis of nonpeptide compounds as mimics of a conformation of methionine-enkephaline

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