Cell-permeable protein inhibitors of calpain
AssigneeNew England Medical Center Hospitals, Inc.
InventorsDavid A. Potter, Paul Skolnik
Life of this patent
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Abstract
Fusion proteins have been discovered that contain a calpastatin peptide and a signal sequence capable of delivering the fusion protein into a cell. These proteins can be used to inhibit calpain and, more specifically, to inhibit platelet aggregation or degranulation, to inhibit or reverse erythrocyte sickling, to inhibit a human immunodeficiency virus (HIV), or to inhibit unwanted cellular proliferation or migration.
Claims29
A method of inhibiting the motility or survival of a cancer cell, the method comprising contacting the cell with an effective amount of fusion protein having a first portion and a second portion, the first portion comprising a signal sequence capable of delivering the fusion protein into the cell and the second portion comprising a calpastatin peptide comprising the sequence Xaa-Xaa-Leu-Gly-Xaa-Xaa-Xaa-Xaa-Thr-Ile-Pro-Pro-Xaa-Tyr-Xaa-Xaa-Leu-Leu-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa (SEQ ID NO:4), wherein
- Xaa at position 1 is Glu, Asp, or Lys;
- Xaa at position 2 is Lys, Glu, Ala, or Asn;
- Xaa at position 5 is Glu, Lys, or Ile
- Xaa at position 6 is Arg, Lys, or Asp;
- Xaa at position 7 is Asp, or Glu;
- Xaa at position 8 is Asp, Val, Ser, Gly, or Glu;
- Xaa at position 13 is Glu, Lys, or Asp;
- Xaa at position 15 is Arg, Lys, or Gln;
- Xaa at position 16 is Glu, His, Lys, or Leu;
- Xaa at position 19 is Glu, Asp, Asn, Ala, or Val;
- Xaa at position 20 is Lys, Asp, Gln, Asn, Thr, or Met;
- Xaa at position 21 is Lys, Asp, Glu, Gly, or Asn;
- Xaa at position 22 is Thr, Glu, Gly, or Lys;
- Xaa at position 23 is Gly, Ala, Glu, Gln, Lys or Asp;
- and
- Xaa at position 24 is Val, Ile, Asp or Gly.
Dependencies are inferred from the claim text.