JP2019503705A - 複数種のアミロイド単量体と凝集体を結合するポリペプチド及びその使用 - Google Patents
複数種のアミロイド単量体と凝集体を結合するポリペプチド及びその使用 Download PDFInfo
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Abstract
Description
Claims (11)
- 複数種のアミロイド単量体と凝集体とを結合するポリペプチドであって、(a)及び/又は(b)で示されるアミノ酸配列を含む、ことを特徴とするポリペプチド。
(a)一般式がSer−X1−Phe−X2−Asn−Lys−Arg(ただし、X1とX2が独立して、20種のアミノ酸のいずれか1種である)であるアミノ酸配列
(b)前記ポリペプチドの機能を有する、(a)の一般式で示されるアミノ酸配列に対して1つ又は複数のアミノ酸残基の置換、欠失又は修飾の付加を行った変異体 - 前記ポリペプチドのアミノ酸配列が、SEQ ID NO.1もしくはSEQ ID NO.2に示すアミノ酸配列、又は、前記ポリペプチドの機能を有する、SEQ ID NO.1もしくはSEQ ID NO.2に示すアミノ酸配列に対して1つもしくは複数のアミノ酸残基の置換、欠失もしくは修飾の付加を行った変異体である、ことを特徴とする請求項1に記載のポリペプチド。
- 前記変異体の配列が、SEQ ID NO.3、SEQ ID NO.4、SEQ ID NO.5またはSEQ ID NO.6である、ことを特徴とする請求項2に記載のポリペプチド。
- 請求項1〜3のいずれか一項に記載のポリペプチドをコードするヌクレオチド配列を含む、ことを特徴とするDNA断片。
- 少なくとも1つのコピーされた請求項4に記載のDNA断片を含む、ことを特徴とする組換えベクター。
- 請求項5に記載の組換えベクターを含む、ことを特徴とする組換え細胞。
- アミロイド細胞毒性阻害剤であって、請求項1〜3のいずれか一項に記載のポリペプチド、請求項4に記載のDNA断片、請求項5に記載の組換えベクター、又は請求項6に記載の組換え細胞のいずれか1種又は少なくとも2種の組み合わせを含み、
好ましくは、前記阻害剤の、Aβ、amylin、インスリン及びリゾチームの細胞毒性の阻害における使用であり、
好ましくは、前記細胞がSH−SY5Y神経芽細胞腫である、ことを特徴とするアミロイド細胞毒性阻害剤。 - アミロイド凝集阻害剤であって、請求項1〜3のいずれか一項に記載のポリペプチド、請求項4に記載のDNA断片、請求項5に記載の組換えベクター、又は請求項6に記載の組換え細胞のいずれか1種又は少なくとも2種の組み合わせを含み、
好ましくは、前記阻害剤の、Aβとリゾチームの凝集の阻害における使用である、ことを特徴とするアミロイド凝集阻害剤。 - 細胞によるAβ除去促進剤であって、請求項1〜3のいずれか一項に記載のポリペプチド、請求項4に記載のDNA断片、請求項5に記載の組換えベクター、又は請求項6に記載の組換え細胞のいずれか1種又は少なくとも2種の組み合わせを含み、
前記細胞が、好ましくはミクログリア細胞であり、より好ましくはBV−2細胞であり、
好ましくは、前記AβがAβ42である、ことを特徴とする細胞によるAβ除去促進剤。 - 医薬組成物であって、請求項1〜3のいずれか一項に記載のポリペプチド、請求項4に記載のDNA断片、請求項5に記載の組換えベクター、又は請求項6に記載の組換え細胞のいずれか1種又は少なくとも2種の組み合わせを含み、
好ましくは、前記医薬組成物が薬学的に許容する補助材料を更に含み、
好ましくは、前記補助材料が賦形剤、希釈剤、ベクター、調味料、バインダー及び充填剤のいずれか1種又は少なくとも2種の組み合わせである、ことを特徴とする医薬組成物。 - 前記医薬組成物の、アミロイドに関する疾患を検出、診断及び/又は治療する医薬の調製における使用であり、
好ましくは、前記疾患がアルツハイマー病、パーキンソン病、ハンチントン舞踏病、又はII型糖尿病のいずれか1種又は少なくとも2種の組み合わせを含む、ことを特徴とする請求項10に記載の医薬組成物。
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