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PEPTIDE FOR CYTOSOLIC DELIVERY

外国特許コード F200010092
整理番号 5685
掲載日 2020年5月15日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2018JP011406
国際公開番号 WO 2018174158
国際出願日 平成30年3月22日(2018.3.22)
国際公開日 平成30年9月27日(2018.9.27)
優先権データ
  • 特願2017-055508 (2017.3.22) JP
発明の名称 (英語) PEPTIDE FOR CYTOSOLIC DELIVERY
発明の概要(英語) The present invention provides a peptide represented by formula (I): R1-IWLTALX5FLGX6X1AAX7X2X3AX8QX4LSX9L-R2 (wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, R1 and R2 are as defined in the description).
従来技術、競合技術の概要(英語) BACKGROUND ART
Protein, a nucleic acid into cells of the introduction of the raw measurement of cellular function, analysis and regulation of cell function is a very useful approach. For example, the current, the fusion fluorescent protein, a variety of intracellular protein localization or behavior has been observed. However, by the fusion fluorescent protein subcellular localization and the influence of the influence on the behavior or activity of a protein cannot be discarded, further, to control the amount of intracellular expression of the fusion protein is difficult. Therefore, these tight in the evaluation, it is desirable that the verification methods. Fusion fluorescent protein fluorescence characteristics and constraints, a suitable chemical fluorophore labeled protein can be introduced into the cell contributes to solve this problem. In addition, in recent years, the use of the native protein to recognize a variety of biosensor and have been developed (Non-Patent Document 1), the measurement cell is expected to be applied to. However, such a chemically modified protein is to be introduced into the cell from outside the cell at a time, in addition to the considerable amount of the protein from the outside of the cell is held in the endosome, the discharge to the cytoplasm, in order to prevent diffusion, these proteins within cells of the visualization and measurement of the desired function is often not possible.
On the other hand, in recent years, a variety of bio-polymer the development of a drug has been in rapid progress. Among these antibodies having specificity for the target is very high, a low-molecular pharmaceutical to the target molecule as an alternative has been the development of the world. However, typically does not transition within the cytoplasm of antibodies, cell membrane receptors on the target or extracellular disease-related factors in the current is limited. Cytoskeletal associated proteins in the cytoplasm and, associated with various factors such as the target for the treatment of disease activity and can be in many cases. Therefore, the efficiency of the polymer in the cell if the introduction is established, the application range of the pharmaceutical antibody greatly enlarged. SiRNA nucleic acid (DNA, RNA) such as further, also in the cells of the target substance is introduced into the pharmaceutical.
As described above, including biologically active protein antibody, nucleic acid, pharmaceutical raw into the cytoplasm of the establishment of a method for effective introduction is demanded.
Endosome cytoplasmic protein or a drug included in the typical discharge unstable peptide as endosome, GALA (non-patent document 2), influenza, the peptide from the protein hemagglutinin (Non-Patent Document 3) HA2 and the like. These are, pH-dependent membrane fusion peptides, and about 5 in pH endosome of the fuzed film formability, which damage the endosomal membrane, cytoplasmic inclusions are released. In addition, known as transmembrane peptide HA2 and peptide HIV-1 Tat peptide (non-patent document 4) as well as the connecting body has been reported, such as Cre and biologically active protein Tat fusion protein used in the cells of the introduced has been reported an example.
In addition, a film having a honeycomb melittin Anuroctoxin in cytotoxicity, basic amino acids lysine maleic acid derivative protected by a pH sensitivity, pH endosome in the desorption of the protecting groups are removed by reduction, to selectively damage the endosomal membrane, cytoplasmic inclusions endosomolysis attempt is released to have been reported (Non-Patent Document 5).
Further, a polycationic polymer such as polyethylene imine proton of the degree of the decrease in the pH rises, induces swelling of the endosome, contents (such as nucleic acid) released into the cytoplasm of the reported (proton sponge effect: Non-Patent Document 6). The pH-sensitive polymer is introduced into the various gene (Patent Document 1) are used.
Patent Document 2 is, including an antibody protein can be introduced into living cells are peptides, the transfer efficiency was room for improvement.
  • 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
  • KYOTO UNIVERSITY
  • 発明者(英語)
  • FUTAKI, Shiroh
  • SAKAMOTO, Kentarou
  • AKISHIBA, Misao
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA 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 KM ML MR NE SN ST TD TG
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