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Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): a new route to cyclic peptides and peptidomimetics.

Publication ,  Journal Article
Shreder, K; Zhang, L; Dang, T; Yaksh, TL; Umeno, H; DeHaven, R; Daubert, J; Goodman, M
Published in: J Med Chem
July 2, 1998

The synthesis and biological activity of a methylamine-bridged enkephalin analogue (MABE) is presented. The key step in the synthesis of the target compound involves the ring opening of Cbz-d-serine beta-lactone with Boc-Phe-NHCH2CH2NHCH3. Further synthetic elaboration of the resulting building block yielded compound 1 (MABE, Tyr-c[(NbetaCH3)-D-A2pr-Gly-Phe-NHCH2CH2-], where A2pr is a 2,3-diaminopropionic acid residue). Utilizing a combination of NMR and molecular modeling, the structure-biological activity relationships for compound 1 were studied. Using an in vitro isolated receptor assay, MABE was found to have affinities for isolated mu delta, and kappa opioid receptors of 1.6, 2.1, and 340 nM, respectively. By an in vivo thermal escape assay, MABE was found to have an ED50 of 0.027 microg in the rat when administered intrathecally. This effect was reversed by naloxone. By comparison, DAMGO, morphine, and DPDPE were found to yield ED50 values of 0.14, 2.4, and 54 microg, respectively, in the same assay.

Duke Scholars

Published In

J Med Chem

DOI

ISSN

0022-2623

Publication Date

July 2, 1998

Volume

41

Issue

14

Start / End Page

2631 / 2635

Location

United States

Related Subject Headings

  • Receptors, Opioid, mu
  • Receptors, Opioid, kappa
  • Receptors, Opioid, delta
  • Rats, Sprague-Dawley
  • Rats
  • Peptides, Cyclic
  • Molecular Mimicry
  • Methylamines
  • Medicinal & Biomolecular Chemistry
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shreder, K., Zhang, L., Dang, T., Yaksh, T. L., Umeno, H., DeHaven, R., … Goodman, M. (1998). Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): a new route to cyclic peptides and peptidomimetics. J Med Chem, 41(14), 2631–2635. https://doi.org/10.1021/jm970861r
Shreder, K., L. Zhang, T. Dang, T. L. Yaksh, H. Umeno, R. DeHaven, J. Daubert, and M. Goodman. “Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): a new route to cyclic peptides and peptidomimetics.J Med Chem 41, no. 14 (July 2, 1998): 2631–35. https://doi.org/10.1021/jm970861r.
Shreder K, Zhang L, Dang T, Yaksh TL, Umeno H, DeHaven R, et al. Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): a new route to cyclic peptides and peptidomimetics. J Med Chem. 1998 Jul 2;41(14):2631–5.
Shreder, K., et al. “Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): a new route to cyclic peptides and peptidomimetics.J Med Chem, vol. 41, no. 14, July 1998, pp. 2631–35. Pubmed, doi:10.1021/jm970861r.
Shreder K, Zhang L, Dang T, Yaksh TL, Umeno H, DeHaven R, Daubert J, Goodman M. Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): a new route to cyclic peptides and peptidomimetics. J Med Chem. 1998 Jul 2;41(14):2631–2635.
Journal cover image

Published In

J Med Chem

DOI

ISSN

0022-2623

Publication Date

July 2, 1998

Volume

41

Issue

14

Start / End Page

2631 / 2635

Location

United States

Related Subject Headings

  • Receptors, Opioid, mu
  • Receptors, Opioid, kappa
  • Receptors, Opioid, delta
  • Rats, Sprague-Dawley
  • Rats
  • Peptides, Cyclic
  • Molecular Mimicry
  • Methylamines
  • Medicinal & Biomolecular Chemistry
  • Male