Chemical conjugation of the neuropeptide kyotorphin and ibuprofen enhances brain targeting and analgesia
dc.contributor.author
dc.date.accessioned
2015-03-23T11:35:12Z
dc.date.available
2015-03-23T11:35:12Z
dc.date.issued
2011-10-03
dc.identifier.issn
1543-8384
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dc.description.abstract
The pharmaceutical potential of natural analgesic peptides is mainly hampered by their inability to cross the blood-brain barrier, BBB. Increasing peptide-cell membrane affinity through drug design is a promising strategy to overcome this limitation. To address this challenge, we grafted ibuprofen (IBP), a nonsteroidal anti-inflammatory drug, to kyotorphin (l-Tyr-l-Arg, KTP), an analgesic neuropeptide unable to cross BBB. Two new KTP derivatives, IBP-KTP (IbKTP-OH) and IBP-KTP-amide (IbKTP-NH 2), were synthesized and characterized for membrane interaction, analgesic activity and mechanism of action. Ibuprofen enhanced peptide-membrane interaction, endowing a specificity for anionic fluid bilayers. A direct correlation between anionic lipid affinity and analgesic effect was established, IbKTP-NH 2 being the most potent analgesic (from 25 μmol·kg -1). In vitro, IbKTP-NH 2 caused the biggest shift in the membrane surface charge of BBB endothelial cells, as quantified using zeta-potential dynamic light scattering. Our results suggest that IbKTP-NH 2 crosses the BBB and acts by activating both opioid dependent and independent pathways
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society (ACS)
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Reproducció digital del document publicat a: http://dx.doi.org/10.1021/mp2003016
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© Molecular Pharmaceutics, 2011, vol. 8, p. 1929-1940
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Articles publicats (D-Q)
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Tots els drets reservats
dc.subject
dc.title
Chemical conjugation of the neuropeptide kyotorphin and ibuprofen enhances brain targeting and analgesia
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/embargoedAccess
dc.embargo.terms
Cap
dc.date.embargoEndDate
info:eu-repo/date/embargoEnd/2026-01-01
dc.relation.projectID
info:eu-repo/grantAgreement/EC/FP7/230654/EU/Selected peptides as drug candidates directed to pain and neurodegeneration/PEP2BRAIN
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
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dc.relation.ProjectAcronym