Conformational and Orientational Guidance of the Analgesic Dipeptide Kyotorphin Induced by Lipidic Membranes: Putative Correlation toward Receptor Docking
The analgesic dipeptide kyotorphin (l-Tyr-l-Arg) and an acylated kyotorphin derivative were studied by a combination of theoretical (molecular dynamics simulation and quantum mechanics methods) and experimental (fluorescence and infrared spectroscopies) approaches both in solution and in model syste...
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Published in | The journal of physical chemistry. B Vol. 110; no. 7; pp. 3385 - 3394 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
23.02.2006
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Subjects | |
Online Access | Get full text |
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Summary: | The analgesic dipeptide kyotorphin (l-Tyr-l-Arg) and an acylated kyotorphin derivative were studied by a combination of theoretical (molecular dynamics simulation and quantum mechanics methods) and experimental (fluorescence and infrared spectroscopies) approaches both in solution and in model systems of membranes. At biological pH the peptides have a neutral net charge. Nevertheless, their phenolic rings interact with phospholipid molecules (partition coefficient varies from 6 × 102 to 2 × 104, depending on the lipid and pH used) despite being exposed to the aqueous bulk medium. The lowest energy transition dipole moment is displaced from the normal to the lipid bilayer by 20° on average. The observed extensive interaction, pK a, precise location, and well-defined orientation in membranes combined with the ability to discriminate rigid raftlike membrane domains suggest that kyotorphin meets the structural constraints needed for receptor−ligand interaction. The acylated kyotorphin derivative mimics kyotorphin properties and represents a promising way for entrapment in a drug carrier and transport across the blood−brain barrier. |
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Bibliography: | ark:/67375/TPS-V4F0VS2R-N istex:6AECD20CC17637862331BA966CB75FD50D655A88 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1520-6106 1520-5207 |
DOI: | 10.1021/jp053651w |