JP3914988B2 - 細胞死誘導のためのペプチドおよび医薬 - Google Patents
細胞死誘導のためのペプチドおよび医薬 Download PDFInfo
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- JP3914988B2 JP3914988B2 JP2003287727A JP2003287727A JP3914988B2 JP 3914988 B2 JP3914988 B2 JP 3914988B2 JP 2003287727 A JP2003287727 A JP 2003287727A JP 2003287727 A JP2003287727 A JP 2003287727A JP 3914988 B2 JP3914988 B2 JP 3914988B2
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Description
Buckley CD, et al.、RGD peptides induce apoptosis by direct caspase-3 activation.、"Nature"、(UK)、1999年、397(6719)巻、p.534-9 Terui Y, et al.、NH2-terminal pentapeptide of endothelial interleukin 8 is responsible for the induction of apoptosis in leukemic cells and has an antitumor effect in vivo.、"Cancer Res. "、1999年、59(22)巻、p.5651-5
本発明のペプチドは、以下の方法によって製造することができる。たとえば、ペプチド合成法によって製造することもできる。また、本発明のペプチドをコードするDNAを含有する形質転換体を培養することによっても製造することができる。
本発明の医薬は、上記ペプチド単独であってもよく、あるいは薬理学的に許容される担体に固定化または混合されていてもよい。このような医薬は、経口的又は非経口的(たとえば、局所、直腸、静脈投与等)に安全に投与することができる。
Fmoc法で固相合成したペプチドをセルロースメンブレンにスポットし、これを直径6mmに切り出して、96穴プレートの底面に入れた。無血清培地DMEM-F-12(Gibco)を使用して、細胞K562(human chronic myelogenous leukemia cell line)を細胞濃度1×105cell/mlに調整し、プレート1wellに対し100μl入れた。この細胞を各チップ上で48時間で培養した(37℃、5% CO2)。蛍光試薬により細胞を染色し、蛍光プレートリーダーFluoroskan Ascent(Labsystems)を用いて培養後の生細胞および細胞死の様子を測定した。蛍光試薬には、生細胞数についてはcalceinAM(molecular probes)(測定:励起485nm、蛍光538nm)、細胞死についてはCytotox one(Promega) (測定:励起560nm、蛍光590nm)を使用した。
上記ペプチドチップにおいて、Fasリガンドのアミノ酸配列を網羅的にスポッティングしたメンブランを使用して、探索した。
Claims (10)
- 配列CNNLPからなるペプチドを含む細胞死誘導剤。
- CNN、CNNL、CNNLPLSH、NNL、NNLP、NNLPL、及びNNNからなる群より選択される配列からなるペプチドを含む細胞死誘導剤。
- 配列CNNXPからなるペプチドを含む細胞死誘導剤、ここで、Xは、アミノ酸I、V、L、F、C、M、A、G、T、S、W、Y、P、H、D、E、N、Q、KまたはRを表す。
- INNLP、VNNLP、CNCLP、TNNLP、CTNLP、及びCNTLPからなる群より選択される配列からなるペプチドを含む細胞死誘導剤。
- 請求項1〜4の何れか1項に記載の細胞死誘導剤を含有する医薬。
- 配列CNNLPからなるペプチドを含む抗癌剤。
- CNN、CNNL、CNNLPLSH、NNL、NNLP、NNLPL、及びNNNからなる群より選択される配列からなるペプチドを含む抗癌剤。
- 配列CNNXPからなるペプチドを含む抗癌剤、ここで、Xは、アミノ酸I、V、L、F、C、M、A、G、T、S、W、Y、P、H、D、E、N、Q、KまたはRを表す。
- INNLP、VNNLP、CNCLP、TNNLP、CTNLP、及びCNTLPからなる群より選択される配列からなるペプチドを含む抗癌剤。
- 請求項6〜9の何れか1項に記載の抗癌剤を含有する医薬。
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