オリゴヌクレオチド・ペプチド複合体:ハイブリッド化による相制御

Jeffrey R Vieregg¹, Michael Lueckheide², Amanda B Marciel¹

¹Institute for Molecular Engineering, University of Chicago , Chicago, Illinois 60637, United States.

Journal of the American Chemical Society

|January 10, 2018

まとめ

核酸の混合状態は,カチオン性ペプチドと複合すると固体沈殿物または液体コアセルバートを形成するかどうかを決定する. この発見は,治療や感知用ナノ粒子を開発する可能性を秘めています.

科学分野:

ポリマー科学
生物物理化学
分子生物学

背景:

反対に電荷を帯びたポリマー混合物における相分離を駆動する.これは解決されていない重要な問題である.
核酸は,高電荷のポリアニオンで,細胞内の基本的なタンパク質 (クロマチン) を介して凝縮し,膜のない臓器を形成します.
治療用ヌクレア酸を納入するためのナノ粒子の組み立てには静電相互作用が鍵となります

研究の目的:

オリゴヌクレオチドとカチオン性ペプチドの間に形成される複合体の相行動を調べる.
核酸の構造と電荷密度が複合体の形成と相分離にどのように影響するかを理解する.
これらの複合体の潜在能力を治療やセンシングの応用に活用する.

主な方法:

オリゴヌクレオチド (RNA,メチルフォスフォナート骨幹) とカチオン性ペプチドによる複合化実験
ポリマーの長さ,濃度,構造が異なる
塩の濃度が複合相に与える影響を研究する.

主要な成果:

核酸の混合状態は複合体の相を制御する.二重鎖は固体沈殿物を形成し,単一鎖は液体コアセルバートを形成する.
単一鎖のオリゴヌクレオチドの低電荷密度は,液体コアセルバートの形成に寄与する.
塩の添加により,沈殿物はコアセルバットに変化し,コアセルバットに結合したオリゴヌクレオチドはハイブリッド化能力を維持する.

結論:

核酸のハイブリッド化状態は,複雑な相行動の決定要因である.
オリゴヌクレオチド複合体は,塩分濃度などの環境刺激に反応して,固体と液体の相の間を切り替えることができる.
これらの発見は,高度な応用のための環境に反応する複合体とナノ粒子を創造する可能性を示唆しています.

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