Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1990-10-05
1992-12-15
Wax, Robert A.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
530325, 530326, 530810, C07K 708, C07K 710, C07K 1700
Patent
active
051718375
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a peptide being capable of binding to interleukin 6, and an adsorbent for interleukin 6 comprising the peptide immobilized on a carrier.
It is known that interleukin 6 (hereinafter abbreviated as IL-6) acts on lymphocytes which are capable of producing an antibody to remarkably enhance productivity of the antibody, and IL-6 is considered to be one of causative agents of autoimmune diseases such as rheumatism and the like. Accordingly, the peptide and the adsorbent of the present invention are useful for treatment of autoimmune diseases such as rheumatism and the like.
PRIOR ART
Science, Vol. 241, pages 825 to 828 (1988) reports that a precursor of human interleukin 6 receptor (hereinafter abbreviated as IL-6 receptor) is composed of 468 amino acids and its primary structure has been elucidated. According to this report, the primary structure of a mature type IL-6 receptor is represented by the formula: ##STR1##
Further, Medical Immunology, Vol. 15, pates 195 to 201 (1988) discloses a report of a relation between IL-6 and autoimmune diseases.
In treatment of autoimmune diseases such as rheumatism and the like, it has been requested to establish means for removing IL-6 which is considered to be a main caustive agent of such diseases. However, any practical method thereof has not yet been established.
One object of the present invention is to provide a novel peptide being capable of binding IL-6. Another object of the present invention is to provide an adsorbent for IL-6 comprising the novel peptide immobilized on a carrier.
DISCLOSURE OF THE INVENTION
According to the present invention, there is provided (1) a peptide being capable of binding to IL-6 represented by the general formula: of X and Y is a single bond or an amino acid residue selected from the group consisting of Asp, Glu, Lys, Ala and a divalent group of the formula: --NH(CH.sub.2).sub.n --CO-- (wherein n is an integer of 1 to 17), or a peptide- segment composed of 2 to 10 amino acid residues selected from the above group which are bound to each other through a peptide bond; Z is hydroxyl group or amino group]. Further, according to the present invention, there is provided (2) an adsorbent comprising the peptide immobilized on a carrier.
In the present specification, various amino acid residues are abbreviated as follows:
Further, in the present specification, the amino acid sequence is described in such a manner that the amino acid residue at the N-terminal is located on the left hand and the amino acid residue at the C-terminal is located on the right hand according to the conventional method.
As the peptide segment represented by X and Y in the general formula (I), for Example, there are the following peptide segments: ##STR2##
When the peptide represented by the general formula (I) wherein X and/or Y are peptide segments composed of 11 or more amino acid residues selected from the above group which are bound to each other through a peptide bond, such a peptide may not have ability to bind the desired IL-6.
Suitable examples of the peptide segment represented by A in the general formula (I) are as follows. The amino acid residues of each peptide segment may be those subjected to homologous substitution. ##STR3##
The peptide represented by the general formula (I) wherein A is a peptide segment formed by bonding 5 or less amino acids has no ability to bind IL-6, or its ability to bind IL-6 is insufficient for the practical use. Further, it is not practical to synthesize a peptide segment being capable of bonding to the desired IL-6 and formed by binding 51 or more amino acids.
The synthesis of the peptide of the general formula (I) can be carried out by the conventional method usually employed in peptide syntheses, for Example, a solid phase synthesis, or a liquid phase synthesis such as stepwise elongation, fragment condensation or the like. In view of the operation, a solid phase synthesis is convenient [see, for Example, Journal of the American Chemical Society, Vol. 85, pages 21
REFERENCES:
patent: 4581010 (1986-04-01), Skurkovich et al.
patent: 4605394 (1986-08-01), Skurkovich
patent: 4737544 (1988-04-01), McCain et al.
Medical Immunology, vol. 15 (2), 1988, (partial translation), pp. 195-201.
Nature, vol. 299, 1982, pp. 793-797, London, GB; M. Noda et al.: "Primary Structure of .alpha.-Subunit Precursor of Torpedo Califonica Acetylcholine Receptor Deduced from cDNA Sequence".
Int. Arch. Allergy Appl. Imunol., vol. 88, 1989, pp. 29-33, Basel, CH, & 17th Int. Symp. of the Collegium Internationale Allergologium, Port-de-France, Mar. 5-10, 1988; T. Hirano et al.: "A Multifunctional Cytokine (IL-6/BSF-2) and Its Receptor".
Science, (Washington, D.C., 1983--), vol. 241, No. 4867, (1988), Katsuhiko Yamasaki et al., [Cloning and Expression of the Human Interleukin-6 (BSF-2/IFN.beta. 2) Receptor], pp. 825-828.
Proc. Jpn. Acad. Ser. B Phys. Biol. Sci., vol. 64, No. 7, (1988), Katsuhiko Yamasaki et al., [Molecular Structure of Interleukin 6 Receptor], pp. 209-211.
T. Creighton, Proteins, pp. 53-54, 1983.
G. Tosato et al., pp. 157-161 in Therapeutic Peptides and Proteins, Marshak and Liu, editors, 1989.
Oka Kiichiro
Tanihara Masao
Kuraray Co. Ltd.
Walsh Stephen
Wax Robert A.
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