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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Use of NMR and Fluorescence Spectroscopy as well as Theoretical Conformational Analysis in Conformation-activity Studies of Cyclic Enkephalin Analogues

Author(s): Joanna Malicka, Cezary Czaplewski, Malgorzata Groth, Wieslaw Wiczk, Stanislaw Oldziej, Leszek Lankiewicz, Jerzy Ciarkowski and Adam Liwo

Volume 4, Issue 1, 2004

Page: [123 - 133] Pages: 11

DOI: 10.2174/1568026043451591

Price: $65


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

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