TOP > 外国特許検索 > PHOSPHORYLATED PEPTIDE, HARD TISSUE AND/OR ECTOPIC CALCIFICATION INHIBITOR, ANTIBODY, AND HARD TISSUE AND/OR ECTOPIC CALCIFICATION PROMOTER

PHOSPHORYLATED PEPTIDE, HARD TISSUE AND/OR ECTOPIC CALCIFICATION INHIBITOR, ANTIBODY, AND HARD TISSUE AND/OR ECTOPIC CALCIFICATION PROMOTER

外国特許コード F130007278
整理番号 F10180
掲載日 2013年4月5日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2012JP067351
国際公開番号 WO 2013005839
国際出願日 平成24年7月6日(2012.7.6)
国際公開日 平成25年1月10日(2013.1.10)
優先権データ
  • 特願2011-150487 (2011.7.6) JP
発明の名称 (英語) PHOSPHORYLATED PEPTIDE, HARD TISSUE AND/OR ECTOPIC CALCIFICATION INHIBITOR, ANTIBODY, AND HARD TISSUE AND/OR ECTOPIC CALCIFICATION PROMOTER
発明の概要(英語) Provided are a phosphorylated peptide having the effect of inhibiting hard tissue and/or ectopic calcification using the active sites for a calcification inhibiting effect of MEPE-derived ASARM peptide, a hard tissue and/or ectopic calcification inhibitor, antibody having a hard tissue and/or ectopic calcification-promoting effect, and a hard tissue and/or ectopic calcification promoter. The phosphorylated peptide is characterized in that the peptide has the entire or partial amino acid sequence of MEPE-derived ASARM peptide, at least two of the amino acid residues in the amino acid sequence are phosphorylated serine, and the peptide has a hard tissue and/or ectopic calcification-inhibiting effect. The antibody is characterized in recognizing phosphorylated serine, which is the active center of the phosphorylated peptide.
従来技術、競合技術の概要(英語) BACKGROUND ART
Calcification of the biological tissue is, for example, bone diseases such as osteoporosis or Osteomalacia calcified hard tissue associated with, or, diabetes, chronic kidney disease is vascular calcification associated with aging or the like included in the ectopic calcification and the like. Such a hard tissue or vascular calcification associated with the prevention of disease, therapeutic agents include, mainly, calcimimetic, vitamin D formulation, estrogen, ipriflavone, calcitonin, a bisphosphonate, vitamin K2 formulation, and the like phosphate adsorbent or statin can be cited.
Is one of the family of proteins (small integrin-binding ligand N-linked glycoproteins) MEPE(Matrix Extracellular Phosphoglycoprotein) SIBLING, low phosphorus in the treatment of neoplastic osteomalacia and proteins found from patients, primarily of bone mineralization (see non-patent document 1) plays a role. For example, in patent document 1, MEPE (a partial peptide thereof, a salt or also including DNA encoding them) from the bone differentiation promoting having an activity, metabolic bone diseases and metabolic cartilage diseases that exhibit low toxicity and safe preventive, therapeutic agents for the use described. In addition, the patent document 2, the production of bone cells such as MEPE protein or its gene as an indicator, a method for evaluating the bone is described. Further, in Patent Document 3, the bone mineral and the like are used MEPE (bone density) is particularly effective in the treatment of the disease in the renal or phosphoric acid to regulate lipid metabolism unit such as described. On the other hand, the knock-out mouse MEPE, bone mass, when the number of osteoblasts because of the increased, a potent inhibitor of bone formation MEPE have been reported (see non-patent document 2).
In addition, MEPE is, cathepsin B is easily cut, and a peptide fragment containing ASARM(acidic serine aspartate rich motif) appears (hereinafter, ASARM peptide). ASARM peptide, the higher the binding affinity of the hydroxyapatite, apatite crystals in vitro in inhibiting the growth of osteoblasts or inhibition of the substrate by calcification and the (see non-patent document 3 and 4). Derived from MEPE ASARM peptide, casein kinase II phosphorylation sites are present. In a recent report, the above described active phosphorylation is presumed to be essential for (see non-patent document 2). In addition, also Patent Document 4, ASARM peptide as described above, bone, soft tissue calcification of the relationship between the teeth and the possibility of, as well as Asp-Glu-Ser-Ser Ser-Ser-Glu-Ser and the amino acid sequence of the associations described.
Protein SIBLING ASARM peptide motifs found in all but, all MEPE ASARM peptide derived from an action similar to that of whether or not the calcification is unknown. In addition, is thought to have endopeptidase activity MEPE PHEX(phosphate-regulating gene with homologies to endopeptidases on the X chromosome) are coupled, and by cathepsin B to suppress decomposition of the MEPE has been reported (see non-patent document 5). On the other hand, non-phosphorylated or phosphorylated ASARM PHEX to bind to the peptides, wherein the peptide phosphorylated ASARM are shown (see non-patent document 2).
Is PHEX, bone (osteoblasts and bone cells) expressed in the teeth (dentin osteoblast) membrane protein, acidosis-low phosphorus-linked X be the causative agent of rickets. A deficiency of that PHEX, its substrate (unidentified, phosphatonin and a provisional name) with a phosphor with an increase in circulating levels of natriuretic factor believed to bring the. In addition, the functional deficit PHEX, phosphatonin, FGF23(fibroblast growth factor 23) natriuretic factor promoting the expression of which is different from the phosphorus has been demonstrated. FGF23 Produced in the bone, kidney function indirectly via factor to suppress bone mineralization. In addition, the effect of such FGF23, such as for example Klotho is associated with the recently it was found that the (non-patent document 6 and non-patent document 7 reference). In addition, also act directly on the bone FGF23 has been suggested.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • HIROSHIMA UNIVERSITY
  • 発明者(英語)
  • YOSHIKO Yuji
  • MINAMIZAKI Tomoko
  • YOSHIOKA Hirotaka
  • HIRATA Isao
  • KOUZAI Katsuyuki
  • MAEDA Norihiko
  • WATANABE Kazuaki
  • SEITO Tsutomu
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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