JP2017507182A - Tmem100ペプチド及びその変異体、並びに疾患又は状態の処置又は予防におけるそれらの使用 - Google Patents
Tmem100ペプチド及びその変異体、並びに疾患又は状態の処置又は予防におけるそれらの使用 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
Description
本特許出願は、2014年2月24日に出願された、その全体において参照によって本明細書中に援用される、米国特許出願第61/943,615号明細書の優先権を主張する。
本発明は、国立衛生研究所によって与えられた、認可番号1R01GM087369によって支持された。政府は、本発明における特定の権利を有する。
高い類似性を有する異なるアミノ酸で置換され、また、特定のアミノ酸配列に、又はアミノ酸をコードする特定の核酸配列に、大いに類似しているとして容易に同定される。任意の特定配列のそのような保存的に置換された変異は、本発明の特徴である。コードされた配列中の単一のアミノ酸又は数%のアミノ酸(一般的に、5%未満、より一般的に、1%未満)を変更、付与又は削除する個々の置換、欠失又は付加は、変更によって、アミノ酸の、化学的に類似したアミノ酸への置換に通じる「保存的に修飾された変異体」である。機能的に類似したアミノ酸を提供する保存的置換テーブルは、当該分野において公知であり、例えば、参照によって本明細書中に援用される、非特許文献2を参照されたい。以下の六つのグループは、互いに対して保存的置換であると考えられるアミノ酸の例示である;1)アラニン(A)、セリン(S)、スレオニン(T)、2)アスパラギン酸(D)、グルタミン酸(E),3)アスパラギン(N)、グルタミン(Q)、4)アルギニン(R)、リジン(K)、5)イソロイシン(I)、ロイシン(L)、メチオニン(M)、バリン(V)、及び6)フェニルアラニン(F)、チロシン(Y)、トリプトファン(W)。
(組成物又は薬物)
%FRET=(CFPpost−CFPpre)/CFPpost
(式中、CFPpost及びCFPpreは、それぞれそのバックグラウンドを差し引いた光脱色後及び光脱色前の細胞内のCFP発光の平均グレー値である)。全画像をImageJで解析した。
Claims (25)
- TRPA1機能に関連された状態を処置又は予防し、低減されたTRPA1活性が重症度を低減させることができる方法であって、有効量のTmem100変異ポリペプチド又はそのフラグメントを投与することを備える、TRPA1機能に関連された状態を処置又は予防し、低減されたTRPA1活性が重症度を低減させることができる方法。
- TRPA1機能に関連された疾患又は状態の症状を予防、処置又は緩和し、低減されたTRPA1活性が重症度を低減させることができる方法であって、それを必要とする対象者に、Tmem100変異ポリペプチド又はそのフラグメントを投与することを備える、TRPA1機能に関連された疾患又は状態の症状を予防、処置又は緩和し、低減されたTRPA1活性が重症度を低減させることができる方法。
- 細胞におけるTRPA1機能を阻害する方法であって、細胞に、有効量のTmem100変異ポリペプチド又はそのフラグメントを投与することを備え、それによって、前記細胞における前記TRPA1機能を阻害する、細胞におけるTRPA1機能を阻害する方法。
- 前記TRPA1機能は、TRPV1と関連がある、請求項1〜3の何れかに記載の方法。
- 前記Tmem100変異ポリペプチド又はそのフラグメントは、TRPA1とTRPV1との関連性を向上させる、請求項4に記載の方法。
- 前記TRPA1機能は、内側TRPA1媒介電流、外側TRPA1媒介電流、TRPA1媒介イオン流出又はTRPA1媒介の神経細胞の過剰興奮性である、請求項1〜3の何れかに記載の方法。
- 前記Tmem100変異ポリペプチドは、配列番号1又は配列番号2のアミノ酸配列或いはそのフラグメントにおける一以上の変異を有するポリペプチドを備える、請求項1〜3の何れかに記載の方法。
- 前記Tmem100変異ポリペプチドは、配列番号5、配列番号6、配列番号7、配列番号8及び配列番号17からなる群より選択されるアミノ酸配列又はそのフラグメントを備える、請求項1〜3の何れかに記載の方法。
- 前記Tmem100変異ポリペプチド又はそのフラグメントは、細胞に供給され、前記細胞は、感覚神経である、請求項1〜8の何れかに記載の方法。
- 前記感覚神経の細胞体は、後根神経節(DRG)にある、請求項9に記載の方法。
- 疼痛の症状を予防、処置又は緩和するために使用される、請求項1〜10の何れかに記載の方法。
- 疥癬の症状を予防、処置又は緩和するために使用される、請求項1〜11の何れかに記載の方法。
- 前記疼痛は、急性疼痛又は慢性疼痛である、請求項12に記載の方法。
- 前記Tmem100変異ポリペプチド又はそのフラグメントは、一以上の薬物と組み合わせて投与される、請求項1〜13の何れかに記載の方法。
- 前記Tmem100変異ポリペプチド又はそのフラグメントは、一以上のTRPV1阻害剤、TRPV3阻害剤、TRPV4阻害剤又はTRPM8阻害剤と組み合わせて投与される、請求項1〜14の何れかに記載の方法。
- TRPA1の活性化に関連する状態を処置又は予防し、低減されたTRPA1活性が重症度を低減させることができる医薬組成物であって、有効量のTmem100変異ポリペプチド又はそのフラグメントを備える、TRPA1の活性化に関連する状態を処置又は予防し、低減されたTRPA1活性が重症度を低減させることができる医薬組成物。
- 前記Tmem100変異ポリペプチドは、配列番号1又は配列番号2のアミノ酸配列或いはそのフラグメントにおける一以上の変異を有するポリペプチドを備える、請求項16に記載の医薬組成物。
- 前記Tmem100変異ポリペプチドは、配列番号5、配列番号6、配列番号7及び配列番号8からなる群より選択されるアミノ酸配列又はそのフラグメントを備える、請求項16に記載の医薬組成物。
- 配列番号5、配列番号6、配列番号7及び配列番号8からなる群より選択されるアミノ酸配列又はそのフラグメントを備える、単離されたポリペプチド。
- 配列番号9、配列番号10、配列番号11及び配列番号12からなる群より選択されるヌクレオチド配列又はそのフラグメントを備える核酸配列によってコードされる、単離されたポリペプチド。
- 配列番号9、配列番号10、配列番号11及び配列番号12からなる群より選択されるヌクレオチド配列又はそのフラグメントを備える、単離された核酸。
- 配列番号5、配列番号6、配列番号7及び配列番号8からなる群より選択されるアミノ酸配列又はそのフラグメントを備えるポリペプチドをコードするヌクレオチド配列を備える、単離された核酸。
- 原核細胞及び真核細胞の少なくとも一つにおいて複製し、請求項21又は22に記載の前記単離された核酸を備える、発現ベクター。
- 請求項23に記載の前記発現ベクターを備えるとともに、前記ポリペプチドを発現する細胞。
- 前記ポリペプチドを発現するために、細胞培養培地中で請求項24に記載の前記細胞を培養することを備える、ポリペプチドを生成する方法。
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