サイト選択的結合のための2-ピリジンカルボックスアルデヒド基を持つアンフィフィリックポリマーを用いたタンパク質の細胞溶融配送

Rapeepat Sangsuwan, Phum Tachachartvanich, Matthew B Francis¹

¹Materials Sciences Division , Lawrence Berkeley National Laboratories , Berkeley , California 94720 , United States.

Journal of the American Chemical Society

|January 22, 2019

まとめ

研究者たちは細胞内に治療用タンパク質を送る新しい生物結合法を開発しましたこのアプローチは機能性タンパク質を細胞溶液に運び,がん治療における治療可能性を高めます.

科学分野:

生物結合化学
分子伝達システム
ガン治療薬

背景:

タンパク質治療は大きな可能性を秘めているが,膜の透過性が悪いため,細胞内での投与は困難である.
現在の方法では,細胞内でのタンパク質の有効性を制限するエンドソーマの捕らわれがしばしば発生します.
標的治療のために機能性タンパク質を細胞細胞溶液に輸送するための効果的な戦略が必要である.

研究の目的:

タンパク質にアンフィフィリックポリマーの部位選択的結合のための新しい生物結合戦略を開発する.
機能性タンパク質を細胞内に効率的に送るため
癌細胞におけるポリマー結合タンパク質の治療可能性を評価する.

主な方法:

2-ピリジンカルボックスアルデヒド基を用いたタンパク質のN端にアンフィフィリックポリマーの部位選択的結合
様々な癌細胞系におけるポリマー-タンパク質結合体の細胞内伝達を追跡するために,イメージング研究を利用する.
細胞内投与後のリボヌクレアゼA (RNase A) の保持活性と細胞毒性効果の評価

主要な成果:

遺伝子組み換えなしにポリマーをタンパク質に結合させるための単純な生物結合法が確立された.
多数の癌細胞の細胞溶液にポリマー-タンパク質の結合物が,おそらく膜融合によって,成功裏に投与されたことが確認された.
結合RNaseAは,その活性を維持し,細胞分泌時に癌細胞に強烈な細胞毒性を示した.

結論:

この生物結合アプローチは,タンパク質ベースの治療薬の細胞内投与のための有望なプラットフォームを提供します.
この方法は,細胞内標的における治療用タンパク質の有効濃度を増やすことで,エンドソーマの捕獲を克服します.
ポリマー結合RNase Aの実証された有効性は,新しいタンパク質ベースのがん治療の開発の可能性を強調しています.

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