Design, Synthesis, and Characterization of Fatty Acid Derivatives of a Dimeric Peptide-Based Postsynaptic Density-95 (PSD-95) Inhibitor

Klaus B Nissen; Julie J Andersen; Linda Maria Haugaard-Kedström; Anders Bach; Kristian Strømgaard

doi:10.1021/jm501755d

Design, Synthesis, and Characterization of Fatty Acid Derivatives of a Dimeric Peptide-Based Postsynaptic Density-95 (PSD-95) Inhibitor

Klaus B Nissen, Julie J Andersen, Linda Maria Haugaard-Kedström, Anders Bach, Kristian Strømgaard

7 Citations (Scopus)

Abstract

Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and inflammatory pain in rodents. To modify the pharmacokinetic profile we designed a series of fatty acid linked dimeric ligands, which potently inhibits PSD-95 and shows improved in vitro blood plasma stability. Subcutaneous administration in rats showed extended stability and sustained release of these ligands. This can facilitate new pharmacological uses of PSD-95 inhibitors and further exploration of PSD-95 as a drug target.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	58
Pages (from-to)	1575-1580
Number of pages	6
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm501755d
Publication status	Published - 12 Feb 2015

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Design, Synthesis, and Characterization of Fatty Acid Derivatives of a Dimeric Peptide-Based Postsynaptic Density-95 (PSD-95) Inhibitor. / Nissen, Klaus B; Andersen, Julie J; Haugaard-Kedström, Linda Maria et al.

In: Journal of Medicinal Chemistry, Vol. 58, 12.02.2015, p. 1575-1580.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and inflammatory pain in rodents. To modify the pharmacokinetic profile we designed a series of fatty acid linked dimeric ligands, which potently inhibits PSD-95 and shows improved in vitro blood plasma stability. Subcutaneous administration in rats showed extended stability and sustained release of these ligands. This can facilitate new pharmacological uses of PSD-95 inhibitors and further exploration of PSD-95 as a drug target.",

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AU - Bach, Anders

AU - Strømgaard, Kristian

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AB - Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and inflammatory pain in rodents. To modify the pharmacokinetic profile we designed a series of fatty acid linked dimeric ligands, which potently inhibits PSD-95 and shows improved in vitro blood plasma stability. Subcutaneous administration in rats showed extended stability and sustained release of these ligands. This can facilitate new pharmacological uses of PSD-95 inhibitors and further exploration of PSD-95 as a drug target.

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Design, Synthesis, and Characterization of Fatty Acid Derivatives of a Dimeric Peptide-Based Postsynaptic Density-95 (PSD-95) Inhibitor

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