Control of transglutaminase catalyzed protein modification by selective irreversible transglutaminase inhibitors

摘要

Specific protein modification catalyzed by transglutaminase (TG) which is controlled by at least one selective, irreversible TG inhibitor (A), is new. Independent claims are also included for: (1) (A) of formula (I); and (2) preparing sidechain-modified peptides, as (A), by replacing, in a peptide known to be a TG substrate, a Glu residue by a modified Glu that has a methyl ketone in the gamma -position. X = diazo, Me2S+, RCOO or RS; Xaa1, Xaa2 = amino protecting group, amino acid (or derivative) or peptide of 2-8, preferably 6-8, amino acids (or derivatives); R = undefined. Provided that the compound acetyl-prolinyl-glutaminyl-prolinyl-(6-diazo-5-oxoleucinyl)leucinyl-prolinyl-phenylalaninyl-NH2 is excluded. [Image].