Peptide thioneamides as selective substrates for cysteine protea

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Peptides with at least one nonpeptide bond other than a...

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530327, 530328, 530329, 530330, 530331, 530332, C07K 502, C07K 702

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047711230

ABSTRACT:
Peptide thioneamides are provided as synthetic substrates for cysteine proteases. The compounds of the invention are peptides consisting of one or more blocked or unblocked amino acids wherein the terminal carboxy of the peptides are thionated and forms a thioneamide linkage with a fluorogenic or chromogenic leaving group. The alpha conbonyls of the remaining amino acids are thionated or unthionated. The invention includes methods and kits for using the peptide thioneamides.

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Campbell et al., "Thionesters as a Probe for Electrophilic Catalysis in the Serine Protease Mechanism," J. Biol. Chem:, vol. 258, pp. 59-66 (1983).
Asboth et al., "Transition-State Stabilization at the Oxyanion Binding Sites of Serine and Thiol Proteinases . . . ," Biochem., vol. 22, pp. 117-122 (1983).
Asboth et al., "Mechanism of Action of Cysteine Proteinases: Oxyanion Binding is Not Essential in the Hydrolysis of Specific Substrates," Biochem., vol. 24, pp. 606-609 (1985).
Clausen et al., "Synthesis of N-Benzyloxycarbonylendothiodipeptide," Tetrahedron, vol. 37, pp. 3635-3639 (1981).
Thorsen et al., "Synthesis of Endothionated Melanostatin Analogs," Tetrahedron, vol. 39, pp. 3429-3435 (1983).
Clausen et al., "Methods for Introducing Thioamide Bonds into the Peptide Backbone . . . " J. Chem. Soc. Perkin Trans. I 1984, pp. 785-798.
Schechter et al., Biochem. Biophys. Res. Comm., vol. 27, pp. 157-162 (1967).

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