Applied Chemistry for Engineering, Vol.31, No.2, 125-137, April, 2020
유기인 계열 독성물질 분해를 위한 바이오스캐빈저 최신 연구 동향
Recent Trend in Bioscavengers for Inactivation of Toxic Organophosphorus Compounds
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초록
최근 몇 년간 유기인 계열 독성물질이 민간인을 대상으로 사용되어 전 세계적으로 큰 위협이 되고 있다. 독성물질에 대한 예방이 불가능한 현 치료대책 대신, 보다 개선된 치료 대책으로서의 바이오스캐빈저에 대한 연구가 활발히 진행됐다. 바이오스캐빈저는 유기인 계열 독성물질이 인체 내 표적 기관에 도달하기 전, 독성물질 자체를 비활성 상태로 전환하거나 독성물질과 기질 간의 결합을 차단함으로써 중독을 예방하는 단백질 및 효소를 일컫는다. 특히 독성물질을 분해하는 과정에서 활성 상태를 유지함으로써 적은 양의 단백질로도 독성물질의 중독을 빠르게 치료하는 촉매성바이오스캐빈저 개발에 많은 노력이 투여되어 왔다. 본 리뷰에서는 촉매성 바이오스캐빈저 개발을 위해 분자진화 및 단백질 공학 기술을 적용한 최신 연구들에 대해 소개하고, 끝으로 이러한 효소들을 임상적으로 승인된 약으로 개발하기 위해 남은 몇 가지 과제들을 간단히 제시할 것이다.
In recent years, toxic organophosphorus compounds (OPs) have been used for civilians, becoming a great threat to the world. Alternative to the current treatment policy unpredictable for any prevention, researches on bioscavenger as an improved treatment have been actively conducted. Bioscavengers refer to proteins and enzymes that prevent intoxication by inactivating or binding toxic OPs before they reaches the target. In particular, extensive efforts have been made to develop catalytic bioscavengers that quickly detoxify OPs even with a small dose of the protein by performing multiple binding and hydrolysis processes with OPs. This review introduces the latest studies and results for developing catalytic bioscavengers using molecular evolution and protein engineering techniques. We will briefly present some of the remaining challenges on developing enzymes into clinically approved drugs.
Keywords:Organophosphorus compounds (OPs);Bioscavengers;Chemical Warfare Agent (CWA);Directed evolution;Protein engineering techniques
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