Synthesis, Biological Activity, and NMR-Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a New α,α-Disubstituted Glycines

Chemical Biology & Drug Design
Anika LasotaAleksandra Olma

Abstract

This article describes new deltorphin I analogs in which phenylalanine residues were replaced by the corresponding (R) or (S)-α-benzyl-β-azidoalanine, α-benzyl-β-(1-pyrrolidinyl)alanine, α-benzyl-β-(1-piperidinyl)alanine, and α-benzyl-β-(4-morpholinyl)-alanine residues. The potency and selectivity of the new analogs were evaluated by a competitive receptor binding assay in the rat brain using [(3) H]DAMGO (a μ ligand) and [(3) H]DELT (a δ ligand). The affinity of analogs containing (R) or (S)-α-benzyl-β-azidoalanine in position 3 to δ-receptors strongly depended on the chirality of the α,α-disubstituted residue. The conformational behavior of peptides modified with (R) or (S)-α-benzyl-β-(1-piperidinyl)Ala, which displays the opposite selectivity, was analyzed by (1) H and (13) C NMR. The μ-selective Tyr-d-Ala-(R)-α-benzyl-β-(1-piperidinyl)Ala-Asp-Val-Val-Gly-NH2 lacks the helical conformation observed in the δ-selective Tyr-d-Ala-(S)-α-benzyl-β-(1-piperidinyl)Ala-Asp-Val-Val-Gly-NH2 . Our results support the proposal that differences between δ- and μ-selective opioid peptides are attributable to the presence or absence of a spatial overlap between the N-terminal message domain and the C-terminal address domain.

References

Apr 3, 1992·Journal of Medicinal Chemistry·L H LazarusW E Wilson
Jan 1, 1992·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·V Erspamer
Jan 1, 1991·Pharmaceutical Research·R S Rapaka, F Porreca
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·V ErspamerG Kreil
Sep 1, 1995·Journal of Biomolecular NMR·D S WishartB D Sykes
Jun 6, 2003·The Journal of Peptide Research : Official Journal of the American Peptide Society·A OlmaA W Lipkowski
Feb 3, 2004·Current Topics in Medicinal Chemistry·Anna JaneckaTomasz Janecki
Mar 11, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·J V AldrichT F Murray
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jun 29, 2004·Biochemical and Biophysical Research Communications·Jakub FichnaAnna Janecka
Aug 18, 2004·IEEE Transactions on Bio-medical Engineering·Peter beim Graben, Stefan Frisch
Oct 12, 2004·Journal of Peptide Science : an Official Publication of the European Peptide Society·Laura BiondiRaniero Rocchi
Feb 7, 2006·Journal of Molecular Graphics & Modelling·Junmei WangDavid A Case
Sep 12, 2006·Pain·Noufissa Kabli, Catherine Marie Cahill
Sep 30, 2009·Journal of Peptide Science : an Official Publication of the European Peptide Society·Dominika WilczyńskaAleksandra Olma
Sep 21, 2010·The Journal of Physical Chemistry. B·Kwang-Im OhMinhaeng Cho
Mar 26, 2013·European Journal of Medicinal Chemistry·Krzysztof BańkowskiJan Izdebski
Jan 6, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Anika LasotaAleksandra Olma

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Citations

Jul 23, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Maciej MaciejczykAleksandra Olma

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