The present disclosure provides fish-derived peptides with ACE inhibitory activity, and methods of producing peptide isolates comprising the fish-derived peptides. The present disclosure also provides pharmaceutical products, dietary supplements, and functional foods including the peptide isolates, and method of lowering blood pressure of a subject by administering to the subject one or more of the fish-derived peptides.

The present invention relates to methods for administering therapeutic doses of bispecific T-cell engaging molecules for the treatment of cancer in a patient. The administration methods reduce the incidence and/or severity of adverse events, such as cytokine release syndrome, and entail administering to a patient a priming dose of the bispecific T-cell engaging molecule by continuous intravenous infusion over a period of days followed by administration of a therapeutic dose of the bispecific T-cell engaging molecule by a bolus intravenous infusion at dosing intervals of at least a week.

Compositions and methods are presented for prevention and/or treatment of a coronavirus disease wherein the composition comprises a recombinant entity. The recombinant entity comprises a nucleic acid that encodes a nucleocapsid protein of coronavirus 2 (CoV2); and/or wherein the recombinant entity encodes a spike protein of CoV2.

An ACE2-Fc hybrid construct is used as a therapeutic and/or analytic entity to treat an individual infected with a coronavirus or to detect a coronavirus in an analyte. In selected embodiments, the Fc portion of the hybrid construct is an IgA Fc portion, and in still further embodiments the ACE2 portion has a mutation that reduces or abolishes ACE2 catalytic activity.

A chimeric protein having deubiquitinase activity, methods of identifying anti-deubiquitinase compounds using chimeric proteins, and kits comprising chimeric proteins are described herein. In one aspect, a chimeric protein comprises a mammalian deubiquitinase catalytic domain, a linker domain, and a non-human deubiquitinase proteasome binding domain. In another aspect, a method of identifying a compound having deubiquitinase inhibition activity comprises a) providing an assay for identifying a compound having deubiquitinase inhibition activity, wherein the assay comprises one or more biological cells comprising a chimeric protein comprising a mammalian deubiquitinase catalytic domain, a linker domain, and a non-human deubiquitinase proteasome binding domain; b) screening the assay with at least one compound; and c) identifying a compound having deubiquitinase inhibition activity based on survival of the biological cell. In another aspect, a kit comprises a biological cell comprising a herein disclosed chimeric protein.

A chimeric protein having deubiquitinase activity, methods of identifying anti-deubiquitinase compounds using chimeric proteins, and kits comprising chimeric proteins are described herein. In one aspect, a chimeric protein comprises a mammalian deubiquitinase catalytic domain, a linker domain, and a non-human deubiquitinase proteasome binding domain. In another aspect, a method of identifying a compound having deubiquitinase inhibition activity comprises a) providing an assay for identifying a compound having deubiquitinase inhibition activity, wherein the assay comprises one or more biological cells comprising a chimeric protein comprising a mammalian deubiquitinase catalytic domain, a linker domain, and a non-human deubiquitinase proteasome binding domain; b) screening the assay with at least one compound; and c) identifying a compound having deubiquitinase inhibition activity based on survival of the biological cell. In another aspect, a kit comprises a biological cell comprising a herein disclosed chimeric protein.

A chimeric protein having deubiquitinase activity, methods of identifying anti-deubiquitinase compounds using chimeric proteins, and kits comprising chimeric proteins are described herein. In one aspect, a chimeric protein comprises a mammalian deubiquitinase catalytic domain, a linker domain, and a non-human deubiquitinase proteasome binding domain. In another aspect, a method of identifying a compound having deubiquitinase inhibition activity comprises a) providing an assay for identifying a compound having deubiquitinase inhibition activity, wherein the assay comprises one or more biological cells comprising a chimeric protein comprising a mammalian deubiquitinase catalytic domain, a linker domain, and a non-human deubiquitinase proteasome binding domain; b) screening the assay with at least one compound; and c) identifying a compound having deubiquitinase inhibition activity based on survival of the biological cell. In another aspect, a kit comprises a biological cell comprising a herein disclosed chimeric protein.

The invention relates to a method for purifying proteins having a tubulin carboxypeptidase activity from a biological extract, comprising polymerization/depolymerization cycle performed on a biological extract in presence of microtubules. The invention further relates to a peptidic based inhibitor for use in the treatment of a disorder involving altered microtubule detyrosination in an animal, wherein the peptidic based inhibitor comprises a peptidic moiety constituted of 1 to 20 amino acids, said peptidic moiety having an amino acid selected from Y or F at the C-terminal position, and wherein the peptidic based inhibitor inhibits at least partially a tubulin carboxypeptidase activity.

Inhibitors of USP30 and methods of using inhibitors of USP30 are provided. In some embodiments, methods of treating conditions involving mitochondrial defects are provided.

The present invention is related to a compound comprising a cyclic peptide of formula (I)

##STR00001## and an N-terminal modification group A attached to Xaa1, wherein Xaa1, Xaa2, Xaa3, Xaa4, Xaa5 and Xaa6 are each residues of an amino acid, Xaa7 is a residue of an amino thiol or an amino acid of formula, Yc is a cyclization element which is either present or absent, and the N-terminal modification group A is either a blocking group Abl or an amino acid Aaa.