Adsorbent adsorbing antibody against β1 adrenoreceptor
View Patent ↗The present invention provides a peptide which selectively adsorbs an anti-β1 adrenoreceptor antibody being one of the contributing factors in dilated cardiomyopathy. The peptide of the invention can be immobilized on a carrier in a short period of time with rarely inducing side reactions, and adsorbent for adsorbing an anti-β1 adrenoreceptor antibody can be produced with good efficiency by using the peptide. In addition, the present invention provides an adsorbent comprising such peptide immobilized on a carrier, an adsorber wherein such adsorbent is used, and a method for adsorbing an anti-β1 adrenoreceptor antibody. The adsorbent and adsorber according to the invention can efficiently deprive an anti-β1 adrenoreceptor antibody-containing liquid, in particular body fluid, of the antibody.
1. A peptide
which comprises an amino acid sequence represented by the following formula (I):
x00-x01-x02-x03-x04-x05-x06-x07-x08-x09-x10-x11-x12-x13 (I)
wherein
x00=Cys, Cys derivative, acetyl or deletion;
x01=Asp, Gln, Thr or deletion;
x02=Trp, Tyr or Thr;
03=Gly;
x04=Thr or Ser;
x05=Leu or Phe;
x06=Val or Phe;
x07=Thr;
x08=Gly, Asp or Glu;
x09=Phe or Leu;
x10=Trp;
x11=Gln, Gln, Thr or Leu;
x12=Tyr, Thr or Ser;
x13=Cys or Cys derivative or deletion;
provided that one of x00 and x13 is Cys or Cys derivative and the other denotes deletion, and optionally a carrier.
2. A peptide
which comprises an amino acid sequence represented by the following formula (II):
y00-y01-y02-y03-y04-y05-y06-y07-y08-y09-y10-y11-y12-y13-y14-y15-y16-y17-y18-y19-y20 (II)
wherein
y00=Cys, Cys derivative or deletion;
y01=His, Glu or Gln;
y02=Trp;
y03=His Phe, Tyr or Trp;
y04=Arg;
y05=Ala or Val;
y06=Gly, Thr, Glu, Ser, Asp or Asn;
y07=Ser, His or Ala;
y08=Asp, Asn, Gln or Glu;
y09=Gly, Ala or deletion;
y10=Glu;
y11=Ala;
y12=Arg;
y13=Asp, Asn or Arg;
y14=Ala;
y15=His, Phe, Trp or Tyr;
y16=Ala, Asp, Asn or Ser;
y17=Asp or Asn;
y18=Glu or Pro;
y19=Arg, Lys or Thr;
y20=Cys, Cys derivative or deletion;
provided that one of y00 and y20 is Cys or Cys derivative and the other denotes deletion, and optionally a carrier.
3. A peptide
which comprises an amino acid sequence represented by the following formula (II):
z00-z01-z02-z03-z04-z05-z06-z07-z08-z09-z10-z11-z12-z13-z14-z15-z16-z17-z18 (III)
wherein
z00=Cys, Cys derivative or deletion;
z01=Ala;
z02=Arg;
z03=Arg, Asp or Asn;
z04=Ser, Ala, Thr or Met;
z05=Tyr, His, Phe or Trp;
z06=Asn, Ala, Asn or Ser;
z07=Asp or Asn;
z08=Pro or Glu;
z09=Lys, Thr or Arg;
z10=Ser, Ala, Thr or Met;
z11=Ser, Thr, Ala or Met;
z12=Asp or Asn;
z13=Phe, Leu or Val;
z14=Val or Leu;
z15=Thr or Ser;
z16=Ser, Asp, Ala or Asn;
z17=Arg, Asp or Asn;
z18=Cys, Cys derivative or deletion;
provided that one of z00 and z18 is Cys or Cys derivative and the other denotes deletion, and optionally a carrier.
4. An adsorbent for an anti-β1 adrenoreceptor antibody
which comprises at least one peptide selected from the group consisting of the peptides according to claim 1 immobilized on a carrier.
5. An adsorbent for an anti-β1 adrenoreceptor antibody
which comprises the peptide according to claim 1 and a peptide
which comprises an amino acid sequence represented by the following formula (II)
y00-y01-y02-y03-y04-y05-y06-y07-y08-y09-y10-y11-y12-y13-y14-y15-y16-y17-y18-y19-y20 (II)
wherein
y00=Cys, Cys derivative or deletion;
y01=His, Glu or Gln;
y02=Trp;
y03=His Phe, Tyr or Trp;
y04=Arg;
y05=Ala or Val;
y06=Gly, Thr, Glu, Ser, Asp or Asn;
y07=Ser, His or Ala;
y08=Asp, Asn, Gln or Glu;
y09=Gly, Ala or deletion;
y10=Glu;
y11=Ala;
y12=Arg;
y13=Asp, Asn or Arg;
y14=Ala;
y15=His, Phe, Trp or Tyr;
y16=Ala, Asp, Asn or Ser;
y17=Asp or Asn;
y18=Glu or Pro;
y19=Arg, Lys or Thr;
y20=Cys, Cys derivative or deletion;
provided that one of y00 and y20 is Cys or Cys derivative and the other denotes deletion, each immobilized on a carrier.
6. An adsorbent for an anti-β1 adrenoreceptor antibody
which comprises the peptide according to claim 1 and a peptide
which comprises an amino acid sequence represented by the following formula (III);
z00-z01-z02-z03-z04-z05-z06-z07-z08-z09-z10-z11-z12-z13-z14-z15-z16-z17-z18 (III)
wherein
z00=Cys, Cys derivative or deletion;
z01=Ala;
z02=Arg;
z03=Arg, Asp or Asn;
z04=Ser, Ala, Thr or Met;
z05=Tyr, His, Phe or Trp;
z06=Asn, Ala, Asn or Ser;
z07=Asp or Asn;
z08=Pro or Glu;
z09=Lys, Thr or Arg;
z10=Ser, Ala, Thr or Met;
z11=Ser, Thr, Ala or Met;
z12=Asp or Asn;
z13=Phe, Leu or Val;
z14=Val or Leu;
z15=Thr or Ser;
z16=Ser, Asp, Ala or Asn;
z17=Arg, Asp or Asn;
z18=Cys, Cys derivative or deletion;
provided that one of z00 and z18 is Cys or Cys derivative and the other denotes deletion, each immobilized on a carrier.
7. An adsorber for an anti-β1 adrenoreceptor antibody
which comprises the adsorbent according to claim 4 as contained in a container having an inlet and outlet for an anti-β1 adrenoreceptor antibody-containing liquid and equipped with means for preventing, the adsorbent from flowing out of the container.
8. A method for adsorbing an anti-β1 adrenoreceptor antibody
which comprises the step of bringing an anti-β1 adrenoreceptor antibody-containing liquid into contact with the adsorbent according to claim 4 .
9. The method according to claim 8 ,
wherein the anti-β1 adrenoreceptor antibody-containing liquid is a body fluid.
10. An adsorbent for an anti-β1 adrenoreceptor antibody
which comprises at least one peptide selected from the group consisting of the peptides according to claim 2 immobilized on a carrier.
11. An adsorbent for an anti-β1 adrenoreceptor antibody
which comprises at least one peptide selected from the group consisting of the peptides according to claim 3 immobilized on a carrier.
12. An adsorber for an anti-β1 adrenoreceptor antibody
which comprises the adsorbent according to claim 5 as contained in a container having an inlet and outlet for an anti-β1 adrenoreceptor antibody-containing, liquid and equipped with means for preventing the adsorbent from flowing out of the container.
13. An adsorber for an anti-β1 adrenoreceptor antibody
which comprises the adsorbent according to claim 6 as contained in a container having an inlet and outlet for an anti-β1 adrenoreceptor antibody-containing liquid and equipped with means for preventing the adsorbent from flowing out of the container.
14. An adsorber for an anti-β1 adrenoreceptor antibody
which comprises the adsorbent according to claim 10 as contained in a container having an inlet and outlet for an anti-β1 adrenoreceptor antibody-containing, liquid and equipped with means for preventing the adsorbent from flowing out of the container.
15. An adsorber for an anti-β1 adrenoreceptor antibody
which comprises the adsorbent according to claim 11 as contained in a container having an inlet and outlet for an anti-β1 adrenoreceptor antibody-containing liquid and equipped with means for preventing the adsorbent from flowing out of the container.
16. A method for adsorbing an anti-β1 adrenoreceptor antibody which comprises the step of bringing an anti-β1 adrenoreceptor antibody-containing liquid into contact with the adsorbent according to claim 5 .
17. A method for adsorbing an anti-β1 adrenoreceptor antibody which comprises the step of bringing an anti-β1 adrenoreceptor antibody-containing liquid into contact with the adsorbent according to claim 6 .
18. A method for adsorbing an anti-β1 adrenoreceptor antibody which comprises the step of bringing an anti-β1 adrenoreceptor antibody-containing liquid into contact with the adsorbent according to claim 10 .
19. A method for adsorbing an anti-β1 adrenoreceptor antibody which comprises the step of bringing an anti-β1 adrenoreceptor antibody-containing liquid into contact with the adsorbent according to claim 11 .
20. The method according, to claim 16 ,
wherein the anti-β1 adrenoreceptor antibody-containing liquid is a body fluid.