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Journal of the Korean Chemical Society (JKCS)

ISSN 1017-2548(Print)
ISSN 2234-8530(Online)
Volume 42, Number 1
JKCSEZ 42(1)
February 20, 1998 

 
Title
NMR Studies of Anticancer Drug Tallysomycin Metal Complexes and its Coordination Modes

핵자기 공명법에 의한 항암제 Tallysomycin 금속착물 합성과 배위구조에 관한 연구
Author
Hoshik Won

원호식
Keywords
Abstract
항암제 금속착물(Metallo-tallysomycin)은 특이한 암세포를 인식하고 비공유결합 형태로 DNA의 염기서열에 결합하여 서열을 균열시킨다. 금속착물의 기능을 이해하기 위해 금속결합 항암제 금속착물(Zn,Co-tallysomycin)를 합성하고 정제 하였다. 최적 pH조건을 찾고 온도의존 NMR실험을 시행하여 교환가능한 1H-NMR 신호를 지정하였다. 최근에 개발된 NERD(2D NOESY 1-1 echo)실험을 통하여 용액상에서의 착물의 결합양식과 구조에 관한 정보를 얻었다.β-aminoalanine, β-hydroxyhistidine, imidazole, 그리고 pyrimidine고리의 질소원자들이 Zn(Ⅱ)이온과 결합하고 있으며, Co(Ⅲ)이온의 경우는 각각 1당량과 2당량의 tallysomycin과 결합할 수 있다는 사실이 밝혀졌다.

Metallo-tallysomycin (an anticancer drug metal complex) recognizes specific tumor cell, and noncovalently binds to DNA base pair to cleave sequence. Anticancer drug metal complexes, zinc- and cobalt-binding tallysomycins, were synthesized and purified in order to understand the functions of metal complexes. Complete exchangeable 1H-NMR signal assignment was accomplished by optimal pH- and temperature-dependent 1H-NMR studies. In addition, a recently developed NERD (2D NOESY-1-1 echo) experiment gave a detail structural feature which is useful for NMR-based solution state structure determination of complex. Results exhibit that nitrogen atoms of β-aminoalanine, β-hydroxyhistidine, imidazole, and pyrimidine ring are the metal binding sites with a Zn(Ⅱ) ion, whereas Co(Ⅲ) ion can bind to one and two equivalent of tallysomycin, respectively.

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