JP2017526647A - Ang−(1−7)誘導体オリゴペプチド、ならびにそれを使用および作製するための方法 - Google Patents
Ang−(1−7)誘導体オリゴペプチド、ならびにそれを使用および作製するための方法 Download PDFInfo
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Abstract
Description
用語「天然」は、部分的または完全なレトロ、インベルソまたはレトロ−インベルソ類似体を調製するための開始配列または参照として用いられるLアミノ酸の任意の配列を指す。したがって、用語「天然Ang−(1−7)」は、内因性Ang−(1−7)の場合と同じアミノ酸配列を有するオリゴペプチドを指す。用語「天然」の使用が天然起源であることを決して意味しないが、天然起源のAng−(1−7)を含み得ることは理解されるべきである。用語「天然」はあくまで、アミノ酸残基の任意の修飾を伴わない、Ang−(1−7)の場合と同じアミノ酸配列を有することを指す。したがって、用語「天然Ang−(1−7)」は、アミノ酸残基が同じでかつ修飾されない限り、合成Ang−(1−7)および天然起源Ang−(1−7)の双方を含む。
下記式のオリゴペプチド誘導体:
A1−A2−A3−A4−A5−A6−A7−A8 (配列番号1)
式中、
A1は、アスパラギン酸、グルタミン酸、アラニン、およびそれらの誘導体からなる群より選択され;
A2は、アルギニン、ヒスチジン、リジン、およびそれらの誘導体からなる群より選択され;
A3は、バリン、アラニン、イソロイシン、ロイシン、およびそれらの誘導体からなる群より選択され;
A4は、チロシン、フェニルアラニン、トリプトファン、およびそれらの誘導体からなる群より選択され;
A5は、イソロイシン、バリン、アラニン、ロイシン、およびそれらの誘導体からなる群より選択され;
A6は、ヒスチジン、アルギニン、リジン、およびそれらの誘導体からなる群より選択され;
A7は、プロリン、グリシン、セリン、およびそれらの誘導体からなる群より選択され;かつ
A8は、存在してもまたは不在であってもよく、A8が存在する場合、A8はセリン、トレオニン、ヒドロキシプロリン、およびそれらの誘導体からなる群より選択され、但し、A8が不在である場合、
(a)A1〜A7の少なくとも1つは単糖または二糖で置換されている、
(b)A7はアミノ基で終結される、あるいは
(c)それらの組合せである。
A1〜A7の少なくとも1つが単糖または二糖で置換されている、実施形態1に記載のオリゴペプチド誘導体。
前記単糖または二糖の少なくとも1つが、グルコース、ガラクトース、キシロース、フコース、ラムノース、ラクトース、セロビオース、メリビオースを含む、実施形態1に記載のオリゴペプチド誘導体。
A8がセリンまたはその誘導体である、実施形態1に記載のオリゴペプチド誘導体。
(i)A8がアミノ基で終結される;または(ii)A8が不在であり、かつA7がアミノ基で終結される、実施形態1に記載のオリゴペプチド誘導体。
(i)A8がグルコースもしくはラクトースでグリコシル化されたセリンである;または(ii)A8が不在であり、かつA7がグルコースもしくはラクトースでグリコシル化されたセリンである、実施形態5に記載のオリゴペプチド誘導体。
A8が不在であり、かつA7がグルコースでグリコシル化されている、実施形態6に記載のオリゴペプチド誘導体。
A1がアスパラギン酸であり;A2がアルギニンであり;A3がバリンであり;A4がチロシンであり;A5がイソロイシンであり;A6がヒスチジンであり;および(i)A8が不在であり、かつA7がアミノ基で終結されるかまたはグリコシル化セリンである、あるいは(ii)A8がアミノ基で終結されたセリンである、実施形態1に記載のオリゴペプチド誘導体。
A8がグリコシル化セリンである、実施形態8に記載のオリゴペプチド誘導体。
A8が不在であり、かつA7がアミノ基で終結されたグリコシル化セリンである、実施形態8に記載のオリゴペプチド誘導体。
配列番号1;配列番号3、配列番号4、配列番号5、配列番号6、配列番号7、配列番号8、配列番号9、配列番号10、配列番号11、配列番号12および配列番号13からなる群より選択される、実施形態1に記載のオリゴペプチド誘導体。
7もしくは8つのアミノ酸を有するグリコシル化Ang−(1−7)誘導体。
キシロース、フコース、ラムノース、グルコース、ラクトース、セロビオース、メリビオース、またはそれらの組合せでグリコシル化されている、実施形態12に記載のグリコシル化Ang−(1−7)誘導体。
前記グリコシル化Ang−(1−7)誘導体のカルボキシル酸末端がアミノ基で置換されている、実施形態12に記載のグリコシル化Ang−(1−7)誘導体。
患者において認知障害を治療するための方法であって、かかる治療を必要とする患者に、治療有効量の実施形態1に記載のオリゴペプチドを投与するステップを含む、方法。
患者において認知障害を治療するための方法であって、かかる治療を必要とする患者に、治療有効量の実施形態12に記載のグリコシル化Ang−(1−7)誘導体を投与するステップを含む、方法。
Claims (16)
- 下記式のオリゴペプチド誘導体:
A1−A2−A3−A4−A5−A6−A7−A8 (配列番号1)
式中、
A1は、アスパラギン酸、グルタミン酸、アラニン、およびそれらの誘導体からなる群より選択され;
A2は、アルギニン、ヒスチジン、リジン、およびそれらの誘導体からなる群より選択され;
A3は、バリン、アラニン、イソロイシン、ロイシン、およびそれらの誘導体からなる群より選択され;
A4は、チロシン、フェニルアラニン、トリプトファン、およびそれらの誘導体からなる群より選択され;
A5は、イソロイシン、バリン、アラニン、ロイシン、およびそれらの誘導体からなる群より選択され;
A6は、ヒスチジン、アルギニン、リジン、およびそれらの誘導体からなる群より選択され;
A7は、プロリン、グリシン、セリン、およびそれらの誘導体からなる群より選択され;かつ
A8は、存在してもまたは不在であってもよく、A8が存在する場合、A8はセリン、トレオニン、ヒドロキシプロリン、およびそれらの誘導体からなる群より選択され、但し、A8が不在である場合、
(a)A1〜A7の少なくとも1つは単糖または二糖で置換されている、
(b)A7はアミノ基で終結される、あるいは
(c)それらの組合せである。 - A1〜A7の少なくとも1つが単糖または二糖で置換されている、請求項1に記載のオリゴペプチド誘導体。
- 前記単糖または二糖の少なくとも1つが、グルコース、ガラクトース、キシロース、フコース、ラムノース、ラクトース、セロビオース、メリビオースを含む、請求項1に記載のオリゴペプチド誘導体。
- A8がセリンまたはその誘導体である、請求項1に記載のオリゴペプチド誘導体。
- (i)A8がアミノ基で終結される;または(ii)A8が不在であり、かつA7がアミノ基で終結される、請求項1に記載のオリゴペプチド誘導体。
- (i)A8がグルコースもしくはラクトースでグリコシル化されたセリンである;または(ii)A8が不在であり、かつA7がグルコースもしくはラクトースでグリコシル化されたセリンである、請求項5に記載のオリゴペプチド誘導体。
- A8が不在であり、かつA7がグルコースでグリコシル化されている、請求項6に記載のオリゴペプチド誘導体。
- A1がアスパラギン酸であり;A2がアルギニンであり;A3がバリンであり;A4がチロシンであり;A5がイソロイシンであり;A6がヒスチジンであり;および(i)A8が不在であり、かつA7がアミノ基で終結されるかまたはグリコシル化セリンである、あるいは(ii)A8がアミノ基で終結されたセリンである、請求項1に記載のオリゴペプチド誘導体。
- A8がグリコシル化セリンである、請求項8に記載のオリゴペプチド誘導体。
- A8が不在であり、かつA7がアミノ基で終結されたグリコシル化セリンである、請求項8に記載のオリゴペプチド誘導体。
- 配列番号1;配列番号3、配列番号4、配列番号5、配列番号6、配列番号7、配列番号8、配列番号9、配列番号10、配列番号11、配列番号12および配列番号13からなる群より選択される、請求項1に記載のオリゴペプチド誘導体。
- 7もしくは8つのアミノ酸を有するグリコシル化Ang−(1−7)誘導体。
- キシロース、フコース、ラムノース、グルコース、ラクトース、セロビオース、メリビオース、またはそれらの組合せでグリコシル化されている、請求項12に記載のグリコシル化Ang−(1−7)誘導体。
- 前記グリコシル化Ang−(1−7)誘導体のカルボキシル酸末端がアミノ基で置換されている、請求項12に記載のグリコシル化Ang−(1−7)誘導体。
- 患者において認知障害を治療するための方法であって、かかる治療を必要とする患者に、治療有効量の請求項1に記載のオリゴペプチドを投与するステップを含む、方法。
- 患者において認知障害を治療するための方法であって、かかる治療を必要とする患者に、治療有効量の請求項12に記載のグリコシル化Ang−(1−7)誘導体を投与するステップを含む、方法。
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