Fibrin binding moieties useful as imaging agents
First Claim
Patent Images
1. An isolated polypeptide having the ability to bind to fibrin, the polypeptide comprising the amino acid sequence:
- Cys-X2-X3-X4-X5-X6-X7-X8-Cys (SEQ ID NO;
2), wherein X2 is Pro, Arg, Asn, Asp, Gln, Gly, Phe, Ser, Thr, or Tyr;
X3 is Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val;
X4 is Glu, Gly, Lys, Ser, or Tyr;
X5 is Pro, Asp, Glu, Asn, Gln, Gly, Leu, Lys, Ser, Thr, or Tyr;
X6 is Arg, Gly, or Trp;
X7 is Leu, Ile, Lys, Met, Asn, Gln, Pro, Ser, Thr, or Val; and
X8 is Ile, Leu, Phe, Trp, or Tyr.
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Abstract
The present invention provides binding moieties for fibrin which have a variety of uses wherever detecting, isolating or localizing fibrin, and particularly fibrin as opposed to fibrinogen, is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding fibrin and recognizing the form of polymerized fibrin found in thrombi. In addition, the polypeptides have a slow dissociation rate from fibrin, which improves their ability to form a contrast image at the site of a fibrin clot, making the disclosed binding moieties particularly useful as imaging agents for thrombi.
68 Citations
59 Claims
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1. An isolated polypeptide having the ability to bind to fibrin, the polypeptide comprising the amino acid sequence:
- Cys-X2-X3-X4-X5-X6-X7-X8-Cys (SEQ ID NO;
2), wherein X2 is Pro, Arg, Asn, Asp, Gln, Gly, Phe, Ser, Thr, or Tyr;
X3 is Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val;
X4 is Glu, Gly, Lys, Ser, or Tyr;
X5 is Pro, Asp, Glu, Asn, Gln, Gly, Leu, Lys, Ser, Thr, or Tyr;
X6 is Arg, Gly, or Trp;
X7 is Leu, Ile, Lys, Met, Asn, Gln, Pro, Ser, Thr, or Val; and
X8 is Ile, Leu, Phe, Trp, or Tyr. - View Dependent Claims (2, 3, 4, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)
- Cys-X2-X3-X4-X5-X6-X7-X8-Cys (SEQ ID NO;
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5. An isolated polypeptide having the ability to bind to fibrin, the polypeptide comprising the amino acid sequence:
- X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15 (SEQ ID NO;
1), wherein X1 is Cys, Pro, or Trp;
X2 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val, or if X4 and X12 are not Cys, then X2 may be Cys;
X3 is Ala, Asn, Gln, Gly, Ile, Leu, Met, Phe, Pro, or Thr;
X4 is Cys or another amino acid capable of forming a covalent cross-link to X12;
X5 is Pro, Arg, Asn, Asp, Gln, Gly, Phe, Ser, Thr or Tyr;
X6 is Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Thr, Tyr, or Val;
X7 is Glu, Gly, Lys, Ser, or Tyr;
X8 is Pro, Asp, Glu, Asn, Gln, Glu, Gly, Leu, Lys, Ser, Thr, or Tyr;
X9 is Arg, Gly, or Trp;
X10 is Leu, Ile, Lys, Met, Asn, Gln, Pro, Ser, Thr, or Val;
X11 is Ile, Leu, Phe, Trp, or Tyr;
X12 is Cys or another amino acid capable of forming a covalent cross-link to X4;
X13 is Cys, Gly, Leu, Phe, Pro, Trp, or Tyr;
X14 is Pro, Ala, Gly, Asn, Gln, Lys, Ser, Thr, Tyr, Asp, Glu, or His; and
X15 is Ala, Arg, Asp, Ile, Leu, Met, Phe, Pro, Trp, Val, Asn, Gln, Gly, Ser, Thr, Tyr, or His. - View Dependent Claims (6, 7, 8, 9, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59)
- X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15 (SEQ ID NO;
Specification