Peptidyl Aldehyde Specifically Interacts with Immunosubunit β1i Proteasome: In Vitro and In Vivo Effects.
We studied the effect of β1i-specific peptidyl aldehyde IPSI-001 on proteasome from mammalian cells. In concentrations <1 μM, this agent effectively suppressed immunoproteasome, but only slightly reduced chymotrypsin-like activity of constitutive proteasome. Intraperitoneal administration of this inhibitor to C3H/He mice in a dose of 100 mg/kg induced no significant physiological or behavioral changes, which attested to its considerable therapeutic potential in the treatment of autoimmune neurodegenerative pathologies.
M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
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Kuzina
M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
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Kudriaeva
BioClinicum Research and Development Center, Moscow, Russia.
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Maltseva
M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. belogurov@mx.ibch.ru.
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Belogurov
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D004676:Myelin Basic Protein / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*
D004151:Dipeptides; C541163:IPSI-001; D004676:Myelin Basic Protein; D046988:Proteasome Endopeptidase Complex
autoantigens; immunoproteasome; inhibitor; multiple sclerosis; peptidyl aldehyde