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

TY - JOUR

T1 - Design, Synthesis, and Characterization of Fatty Acid Derivatives of a Dimeric Peptide-Based Postsynaptic Density-95 (PSD-95) Inhibitor

AU - Nissen, Klaus B

AU - Andersen, Julie J

AU - Haugaard-Kedström, Linda Maria

AU - Bach, Anders

AU - Strømgaard, Kristian

PY - 2015/2/12

Y1 - 2015/2/12

N2 - 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.

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.

U2 - 10.1021/jm501755d

DO - 10.1021/jm501755d

M3 - Journal article

C2 - 25590984

SN - 0022-2623

VL - 58

SP - 1575

EP - 1580

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -