Peptide for binding thereto a low density lipoprotein

Details Peptide for binding thereto a low density lipoprotein Peptide for binding thereto a low density lipoprotein

1997-12-18

2000-10-03

Jones, Dwayne C.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 16, 514 17, 514 18, 514 19, 514824, 530328, 530329, 530330, 530331, 530812, 530814, 530815, A61K 3800

Patent

active

061273392

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP/960,734, filed Jun. 21, 1996.


BACKGROUND OF THE INVENTION

1. Field of the Invention
The present invention relate to a peptide for binding thereto a low density lipoprotein (hereinafter, frequently referred to simply as an "LDL") and an adsorbent comprising a water-insoluble carrier having bonded thereto the peptide. More particularly, the present invention is concerned with a peptide for binding thereto an LDL, wherein the peptide has a specific amino acid sequence comprising 2 to 10 amino acid residues including at least one Phe or Trp and at least one Arg or Lys and wherein the peptide has a specific electric charge (E) which is defined by the formula: E=(the number of positive functional groups present in the peptide)-(the number of negative functional groups present in the peptide). Further, the present invention is also concerned with an adsorbent for removing an LDL from a body fluid, comprising a water-insoluble carrier having bonded thereto the peptide. Still further, the present invention is also concerned with a method for removing an LDL from a body fluid, comprising contacting the body fluid with the peptide.
The peptide of the present invention is advantageous in that the peptide not only has an excellent ability to specifically bind thereto an LDL, but also is free from difficult problems, such as the production of a bradykinin, the activation of blood cells, the adsorption of blood cells onto the peptide and the activation of a blood coagulation system, thus leading to a safety in use of the peptide. Therefore, the peptide of the present invention can be advantageously used not only as a reagent for adsorption-removing an LDL from a body fluid, such as whole blood and plasma, but also as a peptide drug or a carrier peptide for a drug for treating a disease caused by an LDL. Further, the peptide of the present invention, which has the ability to bind thereto an LDL, has only 10 amino acid residues or less and, hence, is advantageous not only in that it can be easily prepared at low cost, but also in that it has excellent stability, such as sterilization stability and storage stability. Further, when an adsorbent comprising a water-insoluble carrier having bonded thereto the peptide of the present invention is employed in a blood purification treatment device or the like (which is necessarily used for removing the LDL from the blood of a patient suffering from a disease in which, due to a morbid factor, the LDL concentration of the blood is caused to increase to a level higher than that of the LDL concentration of the blood of a healthy person), the LDL can be efficiently, safely removed to advantage on the patient. In addition, when a soft gel (such as an agarose gel) or a hard gel (such as cross-linked polyvinyl alcohol) is used as the above-mentioned water-insoluble carrier in the adsorbent, the adsorbent can be advantageously used as a gel in liquid chromatography and the like for separating from an LDL-containing liquid the LDL in high purity form.
In the present specification, amino acid residues are represented using abbreviations, as indicated below, approved by IUPAC-IUB Commission on Biochemical Nomenclature (CBN). With respect to amino acids and the like having isomers, those which are represented by the following abbreviations are of either L-form or D-form. Further, the left and right ends of an amino acid sequence of a peptide are, respectively, the N- and C-termini unless otherwise specified.
2. Prior art
It has been known that, among the lipoproteins present in blood, an LDL contains a large amount of cholesterol and therefore is causative of arteriosclerosis. Conventionally, the treatment of a patient suffering from familial hypercholesterolemia, in which the LDL concentration of the blood of the patient is high, is conducted by extracorporeal blood circulation therapy (hereinafter, frequently referred to as an "LDL apheresis") using an adsorbent having the ability to adsorb an LDL, with the result that various symptoms of the patient hav

REFERENCES:
patent: 5464820 (1995-11-01), Burton et al.
O. Wiklund et al., "Cationic Polypeptides In Vitro Association of Low Density Lipoprotein with Arterial Proteoglycans, Fibroblasts, and Arterial Tissue", Sep./Oct. 1990, pp. 695-702, Arteriosclerosis, vol. 10, No. 5.
U. Olsson et al., "Binding of a Synthetic Apolipoprotein B-100 Peptide and Peptide Analogues to Chondroitin 6-Sulfate: Effects of the Lipid Environment", 1993, pp. 1858-1865, Biochemistry, vol. 32, No. 7.
CAPLUS DN 107:192315, Protter et al., WO 8702061 A1, Apr. 9, 1987.
HCAPLUS AN: 1995: 846295, Daniels et al., Mol. Pharmacol., 48(3), pp. 425-432. (abstract), 1995.
HCAPLUS AN: 1994: 672404, Hlavacek et al., Pept. 1992, Proc. Eur. Pept. Symp., 22.sup.nd, 741-2, 1993.
Rudinger, Peptide Homones, Jun. 1976, pp. 1-7.

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