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  • 09월 05일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제120회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Total Synthesis of α-Amanitin Derivative: A Novel Cytotoxic Agent for Antibody Drug Conjugate Payload

2017년 8월 17일 09시 47분 17초
ORGN.O-8 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 10시 : 45분
Organic Chemistry - Oral Presentations of Young Scholars in Organic Division
저자 및
Gangadhar Rao Mathi, Jong Yeon Hwang, jae du ha1, Chang-Soo Yun, Sung Yun Cho1, Hyoung Rae Kim1, PILHO KIM*
Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Korea
1WCI, Korea Research Institute of Chemical Technology, Korea
α-Amanitin belongs to a large group of protoplasmic mushroom toxins known as amatoxin family isolated from the green death cap mushroom Amanita phalloides. α-Amanitin is characterized by a defined rigid structure consisting of a bicyclic octapeptide, with an intraannular linkage known as a tryptathionine bridge between tryptophan and cysteine. The toxin shows remarkable binding affinity for eukaryotic RNA polymerase II. Inhibition of RNA polymerase II compromises cellular homeostasis and leads to apoptosis. Amatoxins are usually isolated from collected amanita phalloides mushrooms or from pure cultures. However the amounts that can be obtained are rather low and the flexibility for further modifications are limited. The use of entirely synthetic routes to amatoxins may offer the supply of large quantities required for therapeutic use. No fully solution phase synthetic approach to the relevant amatoxins has been reported so far. Hence there is high need in the prior art to identify alternate method for synthesizing α-Amanitin and its derivatives. α-Amanitin seems to be a suitable toxic payload for use in an Antibody-Drug Conjugate (ADC) because of the unique mode of action and the molecular characteristics of the toxin. A new α-Amanitin derivative applicable for diverse linker chemistry was designed to improve stability with prolonged cytotoxicity. Retrosynthesis and the utilization of orthogonal protecting groups during the course of total chemical synthesis of α-Amanitin derivative will be presented.