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. 1978 Jan;75(1):7–11. doi: 10.1073/pnas.75.1.7

Energy conformation study of Met-enkephalin and its D-Ala2 analogue and their resemblance to rigid opiates.

G H Loew, S K Burt
PMCID: PMC411171  PMID: 272674

Abstract

Conformational similarities of Met-enkephalin and its D-Ala2 analogue to rigid opiates were studied by both empirical and quantum mechanical methods. By both methods, conformers with maximum resemblance to rigid opiates have the highest energies. Conformers with the lowest energy had no resemblance to rigid opiates. However, several low and intermediate energy conformers were identified in which at least the NH2-terminal tyrosine residue overlaps with the phenethylamine moiety of rigid opiates and which could equally well accommodate either Gly2 or D-Ala2. The conformer among these with greatest additional resemblance to other binding sites of rigid opiates is proposed as the most likely candidate for an induced fit at the receptor site.

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Selected References

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  1. Belluzzi J. D., Grant N., Garsky V., Sarantakis D., Wise C. D., Stein L. Analgesia induced in vivo by central administration of enkephalin in rat. Nature. 1976 Apr 15;260(5552):625–626. doi: 10.1038/260625a0. [DOI] [PubMed] [Google Scholar]
  2. Bradbury A. F., Smyth D. G., Snell C. R. Biosynthetic origin and receptor conformation of methionine enkephalin. Nature. 1976 Mar 11;260(5547):165–166. doi: 10.1038/260165a0. [DOI] [PubMed] [Google Scholar]
  3. Burgen A. S., Roberts G. C., Feeney J. Binding of flexible ligands to macromolecules. Nature. 1975 Feb 27;253(5494):753–755. doi: 10.1038/253753a0. [DOI] [PubMed] [Google Scholar]
  4. Chandrasekaran R., Lakshminarayanan A. V., Pandya U. V., Ramachandran G. N. Conformation of the LL and LD hairpin bends with internal hydrogen bonds in proteins and peptides. Biochim Biophys Acta. 1973 Mar 23;303(1):14–27. doi: 10.1016/0005-2795(73)90143-8. [DOI] [PubMed] [Google Scholar]
  5. Chang J. K., Fong B. T., Pert A., Pert C. B. Opiate receptor affinities and behavioral effects of enkephalin: structure-activity relationship of ten synthetic peptide analogues. Life Sci. 1976 Jun 15;18(12):1473–1481. doi: 10.1016/0024-3205(76)90366-0. [DOI] [PubMed] [Google Scholar]
  6. Coy D. H., Kastin A. J., Schally A. V., Morin O., Caron N. G., Labrie F., Walker J. M., Fertel R., Berntson G. G., Sandman C. A. Synthesis and opioid activities of stereoisomers and other D-amino acid analogs of methionine-enkephalin. Biochem Biophys Res Commun. 1976 Dec 6;73(3):632–638. doi: 10.1016/0006-291x(76)90857-3. [DOI] [PubMed] [Google Scholar]
  7. Feldberg W., Smyth D. G. C-fragment of lipotropin--an endogenous potent analgesic peptide. Br J Pharmacol. 1977 Jul;60(3):445–453. doi: 10.1111/j.1476-5381.1977.tb07521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garbay-Jaureguiberry C., Roques B. P., Oberlin R. Preferential conformation of the endogenous opiate-like pentapeptide Met-enkephalin in DMSO-D6 solution determined by high field H NMR. Biochem Biophys Res Commun. 1976 Jul 26;71(2):558–565. doi: 10.1016/0006-291x(76)90823-8. [DOI] [PubMed] [Google Scholar]
  9. Hiltner W. A., Walton A. G. Energetics of folding of a lysozyme beta-bend. J Mol Biol. 1975 Mar 15;92(4):567–572. doi: 10.1016/0022-2836(75)90310-1. [DOI] [PubMed] [Google Scholar]
  10. Horn A. S., Rodgers J. R. Structural and conformational relationships between the enkephalins and the opiates. Nature. 1976 Apr 29;260(5554):795–797. doi: 10.1038/260795a0. [DOI] [PubMed] [Google Scholar]
  11. Hughes J., Smith T., Morgan B., Fothergill L. Purification and properties of enkephalin - the possible endogenous ligand for the morphine receptor. Life Sci. 1975 Jun 15;16(12):1753–1758. doi: 10.1016/0024-3205(75)90268-4. [DOI] [PubMed] [Google Scholar]
  12. Isogai Y., Némethy G., Scheraga H. A. Enkephalin: conformational analysis by means of empirical energy calculations. Proc Natl Acad Sci U S A. 1977 Feb;74(2):414–418. doi: 10.1073/pnas.74.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacquet Y. F., Marks N. The C-fragment of beta-lipotropin: an endogenous neuroleptic or antipsychotogen? Science. 1976 Nov 5;194(4265):632–635. doi: 10.1126/science.185695. [DOI] [PubMed] [Google Scholar]
  14. Jones C. R., Gibbons W. A., Garsky V. Proton magnetic resonance studies of conformation and flexibility of enkephalin peptides. Nature. 1976 Aug 26;262(5571):779–782. doi: 10.1038/262779a0. [DOI] [PubMed] [Google Scholar]
  15. Momany F. A. Conformational analysis of methionine-enkephalin and some analogs. Biochem Biophys Res Commun. 1977 Apr 25;75(4):1098–1103. doi: 10.1016/0006-291x(77)91495-4. [DOI] [PubMed] [Google Scholar]
  16. Morgan B. A., Smith C. F., Waterfield A. A., Hughes J., Kosterlitz H. W. Structure-activity relationships of methionine-enkephalin. J Pharm Pharmacol. 1976 Aug;28(8):660–661. doi: 10.1111/j.2042-7158.1976.tb02827.x. [DOI] [PubMed] [Google Scholar]
  17. Pert C. B., Pert A., Chang J. K., Fong B. T. (D-Ala2)-Met-enkephalinamide: a potent, long-lasting synthetic pentapeptide analgesic. Science. 1976 Oct 15;194(4262):330–332. doi: 10.1126/science.968485. [DOI] [PubMed] [Google Scholar]
  18. Saran A., Pullman B., Perahia D. Molecular orbital calculations on the conformation of nucleic acids and their constituents. VI. Conformation about the exocyclic C(4')-C(5') bond in alpha-nucleosides. Biochim Biophys Acta. 1973 Apr 11;299(4):497–499. doi: 10.1016/0005-2787(73)90220-7. [DOI] [PubMed] [Google Scholar]
  19. Simantov R., Snowman A. M., Snyder S. H. A morphine-like factor 'enkephalin' in rat brain: subcellular localization. Brain Res. 1976 May 14;107(3):650–657. doi: 10.1016/0006-8993(76)90155-4. [DOI] [PubMed] [Google Scholar]
  20. Simantov R., Snyder H. Isolation and structure identification of a morphine-like peptide "enkephalin" in bovine brain. Life Sci. 1976 Apr 15;18(8):781–787. doi: 10.1016/0024-3205(76)90002-3. [DOI] [PubMed] [Google Scholar]
  21. Simantov R., Snyder S. H. Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2515–2519. doi: 10.1073/pnas.73.7.2515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Venkatachalam C. M. Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers. 1968 Oct;6(10):1425–1436. doi: 10.1002/bip.1968.360061006. [DOI] [PubMed] [Google Scholar]
  23. Walker J. M., Berntson G. G., Sandman C. A., Coy D. H., Schally A. V., Kastin A. J. An analog of enkephalin having prolonged opiate-like effects in vivo. Science. 1977 Apr 1;196(4285):85–87. doi: 10.1126/science.190683. [DOI] [PubMed] [Google Scholar]
  24. Waterfield A. A., Hughes J., Kosterlitz H. W. Cross tolerance between morphine and methionine-enkephalin. Nature. 1976 Apr 15;260(5552):624–625. doi: 10.1038/260624a0. [DOI] [PubMed] [Google Scholar]

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