JP2017000090A - 悪性神経膠腫分子標的ペプチド - Google Patents
悪性神経膠腫分子標的ペプチド Download PDFInfo
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Abstract
Description
(A) 配列番号1又は2で表されるアミノ酸配列からなるペプチド
(B) 配列番号1又は2で表されるアミノ酸配列において、1又は2個のアミノ酸が欠失、置換、挿入及び/又は付加されたアミノ酸配列からなり、且つ脳移行活性及び悪性神経膠腫細胞に選択的に取り込まれる作用を有するペプチド
(C) (A)又は(B)に示されるペプチドのC末端側及び/又はN末端側に、1又は2個の任意のアミノ酸が付加されたアミノ酸配列からなり、且つ脳移行活性及び悪性神経膠腫細胞に選択的に取り込まれる作用を有するペプチド。
本発明のペプチドは、以下の(A)、(B)又は(C)であることを特徴とする。
(A) 配列番号1(NTGSPYE)又は配列番号2(RGATPMS)で表されるアミノ酸配列からなるペプチド
(B) 配列番号1又は2で表されるアミノ酸配列において、1又は2個のアミノ酸が欠失、置換、挿入及び/又は付加されたアミノ酸配列からなり、且つ脳移行活性及び悪性神経膠腫細胞に選択的に取り込まれる作用を有するペプチド
(C) (A)又は(B)に示されるペプチドのC末端側及び/又はN末端側に、1又は2個の任意のアミノ酸が付加されたアミノ酸配列からなり、且つ脳移行活性及び悪性神経膠腫細胞に選択的に取り込まれる作用を有するペプチド。
本発明の悪性神経膠腫送達用キャリア分子は、上記(A)、(B)又は(C)のペプチドを含むことを特徴とする。
本発明の複合体は、上記(A)、(B)又は(C)のペプチド、及びそれに結合した抗癌作用を有する化合物を含有することを特徴とする。
本発明の医薬組成物は、上記の複合体を含むことを特徴とする。
本発明の脳腫瘍の画像診断薬は、上記ペプチドを含むことを特徴とし、造影剤を更に含むことが望ましい。ここで、造影剤としては、画像診断の際に脳腫瘍を可視化することが可能な化合物であれば特に制限無く使用することができる。
滋賀県立成人病センターの倫理委員会の審査・承認を受け手術で摘出した悪性神経膠腫から腫瘍幹細胞株を樹立し、それをSICDマウスの脳に移植し、経時的MRIで増殖−浸潤することを観察した。移植から約2ヶ月後にファージディスプレイライブラリを使用してバイオパニングを実施した。
LB培地 35 g
アガロース 7 g
total volume 蒸留水 1 L
LBアガー 35 g
IPTG/Xgalストック 1 mL
total volume 蒸留水 1 L
IPTG/Xgalストック
IPTG (isopropyl-β-D-thiogalactoside) 1.25 g
Xgal (5-Bromo-4-chloro-3-indolyl-β-D-galactoside) 1 g
N,N-ジメチルホルムアミド 25 mL
NaCl 5.8 g
MgSO47H2O 2 g
1M Tris-HCl(pH7.5) 50 mL
ゼラチン 100 mg
total volume 蒸留水 1 L
LB培地 35 g
total volume 蒸留水 1 L
ポリエチレングリコール-8000 200 g
NaCl 146.1 g
total volume 蒸留水 1 L
生体バイオパニング法により、BT-33及びBT-80は腫瘍血管ではなく腫瘍細胞に特異的に結合するペプチドであることが確認できた。また、BT-33及びBT-80は経静脈投与でヒト悪性神経膠腫細胞に特異的に取り込まれたことから、これらのペプチドは血管を透過できる上に悪性神経膠腫の細胞内に特異的に取り込まれる特徴を有することが分かる。
Claims (8)
- 以下の(A)、(B)又は(C)に記載のペプチド:
(A) 配列番号1又は配列番号2で表されるアミノ酸配列からなるペプチド
(B) 配列番号1又は2で表されるアミノ酸配列において、1又は2個のアミノ酸が欠失、置換、挿入及び/又は付加されたアミノ酸配列からなり、且つ脳移行活性及び悪性神経膠腫細胞に選択的に取り込まれる作用を有するペプチド
(C) (A)又は(B)に示されるペプチドのC末端側及び/又はN末端側に、1又は2個の任意のアミノ酸が付加されたアミノ酸配列からなり、且つ脳移行活性及び悪性神経膠腫細胞に選択的に取り込まれる作用を有するペプチド。 - 前記(C)に示されるペプチドにおいてN末端及びC末端にそれぞれシステイン残基を有し、且つこれらのシステイン残基間でジスルフィド結合を形成している、請求項1に記載のペプチド。
- 請求項1に記載のペプチドをコードする核酸。
- 請求項1又は2に記載のペプチドを含む悪性神経膠腫送達用キャリア分子。
- 請求項1又は2に記載のペプチド、及びそれに結合した抗癌作用を有する化合物を含有する複合体。
- 請求項5に記載の複合体を含む医薬組成物。
- 脳腫瘍の予防及び/又は治療用である、請求項6に記載の医薬組成物。
- 請求項1又は2に記載のペプチドを含む脳腫瘍の画像診断薬。
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