Patent ID: 6197536
Filing Date: 2001-03-06
Classification: C07K,C12N

Abstract:
A depsipeptide consisting of between 8 and 12 amino acid residues and one .alpha.-hydroxy acid, which depsipetide has residues arranged in positions from P6 to P3' in the order P6-P5-P4-P3-P2-P1-P1'-P2'-P3', wherein:the bond between residues P1 and P1' is an ester bond;the residue in the P6 position is an amino acid residue selected from -he group consisting of Asp, Asn, and Glu;the residue in the P5 position is an amino acid residue selected from the group consisting of Glu, Cys, and Asp;the residue in the P4 position is an amino acid residue selected from the group consisting of Met, Ser, and Val;the residue in the P3 position is an amino acid residue selected from the group consisting of Glu, Thr, and Val;the residue in the P2 position is an amino acid residue selected from the group consisting of Met, Pro, and Cys;the residue in the P1 position is 2-aminobutyric acid;the residue in the P1' position is an .alpha.-hydroxy acid residue selected from the group consisting of an .alpha.-hydroxy acid corresponding in structure to Ala and Ser;the residue in the P2' position is an amino acid residue selected from the group consisting of Ser, Gly, Met, and Ala; andthe residue in the P3' position is an amino acid residue selected from the group consisting of His, Ser, Lys, and Ala,wherein:said depsipeptide is cleanable into an N-terminal fragment and a C-terminal fragment by NS3 serine protease of hepatitis C virus (HCV) in said ester bond between residue P1 and residue P1' with a k.sub.cat /K.sub.m greater than 20 M.sup.-1 S.sup.-1 ;the N-terminal residue is optionally modified with an .alpha.-amino protecting group;the C-terminal residue is optionally modified at a side chain or at the carboxyl group;an amino acid residue in said C-terminal fragment portion of said depsipertide is optionally radiolabeled; andoptionally, either (1) an amino acid residue in said N-terminal fragment portion of said depsipeptide is modified with a fluorescent 5-[(2'-aminoethyl)amino]naphthalene-sulfonic acid donor group (EDANS) and an amino acid residue in said C-terminal fragment portion of said depsipeptide is modified with a 4-[[4'-dimethylaminophenyl]azo]benzoic acid acceptor group (DABCYL) or (2) an amino acid residue in said N-terminal fragment portion of said depsipeptide is modified with DABCYL and an amino acid residue in said C-terminal portion of said depsipeptide is modified with EDANS.