Abstract
In this review the conformational studies of natural enkephalins (H-Tyr-Gly-Gly-Phe- Met-OH the [Met5]enkephalin and H-Tyr-Gly-Gly-Phe-Leu-OH; the [Leu5]enkephalin), their acyclic and cyclic analogues, including those carried out in our laboratory, performed by experimental and theoretical methods and their combination, are described. Emphasis is given on the role of conformational constraints introduced by cyclization on activity at the μ and δ opioid receptors. Comparison of the conformations of cyclic enkephalin analogues with high δ-receptor activity with those of potent rigid non-peptide δ-receptor agonists indicates that the proximity of the aromatic side chains in positions 1 and 4 as well as the N-terminal amino group is desirable for the activity at the d opioid receptors; early conformational studies also suggested that spatial separation of the aromatic side chains and rigidity of the cyclic backbone is desirable for μ-receptor activity. The results of our recent conformational studies performed with the use of fluorescence and NMR spectroscopy as well as theoretical calculations indicate, however, that these structural features are not necessary for activity at the m opioid receptors. Methods applied to the determination of the conformation of flexible peptides, such as Nuclear Magnetic Resonance (NMR), fluorescence spectroscopy, and theoretical conformational analysis are also discussed briefly.
Keywords: Fluorescence Spectroscopy, Enkephalin Analogues, H-Tyr-Gly-Gly-Phe-Leu-OH, aromatic
Current Topics in Medicinal Chemistry
Title: Use of NMR and Fluorescence Spectroscopy as well as Theoretical Conformational Analysis in Conformation-activity Studies of Cyclic Enkephalin Analogues
Volume: 4 Issue: 1
Author(s): Joanna Malicka, Cezary Czaplewski, Malgorzata Groth, Wieslaw Wiczk, Stanislaw Oldziej, Leszek Lankiewicz, Jerzy Ciarkowski and Adam Liwo
Affiliation:
Keywords: Fluorescence Spectroscopy, Enkephalin Analogues, H-Tyr-Gly-Gly-Phe-Leu-OH, aromatic
Abstract: In this review the conformational studies of natural enkephalins (H-Tyr-Gly-Gly-Phe- Met-OH the [Met5]enkephalin and H-Tyr-Gly-Gly-Phe-Leu-OH; the [Leu5]enkephalin), their acyclic and cyclic analogues, including those carried out in our laboratory, performed by experimental and theoretical methods and their combination, are described. Emphasis is given on the role of conformational constraints introduced by cyclization on activity at the μ and δ opioid receptors. Comparison of the conformations of cyclic enkephalin analogues with high δ-receptor activity with those of potent rigid non-peptide δ-receptor agonists indicates that the proximity of the aromatic side chains in positions 1 and 4 as well as the N-terminal amino group is desirable for the activity at the d opioid receptors; early conformational studies also suggested that spatial separation of the aromatic side chains and rigidity of the cyclic backbone is desirable for μ-receptor activity. The results of our recent conformational studies performed with the use of fluorescence and NMR spectroscopy as well as theoretical calculations indicate, however, that these structural features are not necessary for activity at the m opioid receptors. Methods applied to the determination of the conformation of flexible peptides, such as Nuclear Magnetic Resonance (NMR), fluorescence spectroscopy, and theoretical conformational analysis are also discussed briefly.
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Malicka Joanna, Czaplewski Cezary, Groth Malgorzata, Wiczk Wieslaw, Oldziej Stanislaw, Lankiewicz Leszek, Ciarkowski Jerzy and Liwo Adam, Use of NMR and Fluorescence Spectroscopy as well as Theoretical Conformational Analysis in Conformation-activity Studies of Cyclic Enkephalin Analogues, Current Topics in Medicinal Chemistry 2004; 4 (1) . https://dx.doi.org/10.2174/1568026043451591
DOI https://dx.doi.org/10.2174/1568026043451591 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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