서지주요정보
NMR studies of anticancer drug and DNA complexes = 항암제와 핵산 복합체의 핵자기 공명 연구
서명 / 저자 NMR studies of anticancer drug and DNA complexes = 항암제와 핵산 복합체의 핵자기 공명 연구 / Jin-Young Park.
저자명 Park, Jin-Young ; 박진영
발행사항 [대전 : 한국과학기술원, 1997].
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8007576

소장위치/청구기호

학술문화관(문화관) 보존서고

DCH 97008

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초록정보

Part Ⅰ The echinomycin complex with the self-complementary DNA decamer $d(ACGTTAACGT)_2$ has been investigated in solution by proton NMR spectroscopy and compared previously reported complexes, 2echinomycin-$[d(CGTACG)]_2$ and 2echinomycin-$[d(ACGTATACGT)]_2$. Echinomycin binds cooperatively as a bisintercalator at the CpG steps. An analysis of the intermolecular NOE patterns defines the position and orientation of the bound drug molecule. The terminal AㆍT base pairs are Hoogsteen base paired, whereas the four AㆍT pairs are clearly Watson-Crick base paired unlike the other complexes. Thus, the presence of the extra AㆍT base pairs between the binding sites appears to prevent the formation of Hoogsteen base pairs immediately adjacent to the binding site. All four central AㆍT base pairs are destabilized relative to those in the free DNA. Because there is no evidence for unwinding of the DNA duplex in the complex relative to the free DNA, we conclude that the hypersensitivity to DNA cleavage reagents distal to echinomycin binding sites might be due to the destabilization of DNA structure induced by the drug binding. Part Ⅱ These hyperreactivity of DNA distal to the echinomycin binding sites can not be well explained by the only structural studies. We study one of another properties through measurement imino proton exchange rate. It is the kinetic property of the DNA base pair. We compare the TTAA and TATA steps with base pair lifetimes in complexes and free DNA duplexes. In the duplexes, TTAA step is more stable than TATA step as a whole. But the trends are opposite. The inner most base pairs in TTAA step are less stable than the next base pairs. In the contrary, the inner most base pairs have the slightly longer lifetimes than the next base pairs. Through making complexes with echinomycin, those trend are not changed in each complex , except for slightly destabilization as a whole. We can propose that the propagated destabilization in our result can also explain that hyperreactivity, and one of the important propagated effects may be the enhanced destabilization(increased flexibility) with the structural deviations(unwinding etc.). Part Ⅲ The local structure of DNA template depends on the sequence. Some specific sequences are recognized by the enzymes to do biological functions. The structures with sequence-specific characters are important to elucidate the interaction of enzyme and DNA. TTAA and TATA are both RNA polymerase binding sites for transcription. For the transcriptional function, the TTAA and TATA steps should be easily unwounded. Because GㆍC base pairs are more stable than AㆍT base pairs, poly AㆍT base pairs may be needed. $(T)_n(A)_n$ and $(TA)_n$ steps may be more easily unwounded than $(A)_n(T)_n$ step due to the stable stacking in $(A)_n(T)_n$. This character may be explained by the structural aspect, stacking, buckling or bending etc., along with the kinetic data. The structural characters of TTAA and TATA steps are well matched to their kinetic data.

서지기타정보

서지기타정보
청구기호 {DCH 97008
형태사항 xii, 120 p. : 삽도 ; 26 cm
언어 영어
일반주기 Includes appendix
저자명의 한글표기 : 박진영
지도교수의 영문표기 : Byong-Seok Choi
지도교수의 한글표기 : 최병석
수록 잡지명 : "NMR Investigation of Echinomycin Binding to d(ACGTTAACGT)$_2$ : Hoogsteen versus Watson-Crick A$\cdot$T Base Pairing between Echinomycin Binding Sites". Journal of Biochemistry. The Japanese Biochemical Society, vol. 118, no. 5, pp. 989-995
학위논문 학위논문(박사) - 한국과학기술원 : 화학과,
서지주기 Includes references
주제 NMR
DNA
Echinomycin
Structure
Kinetics
핵자기공명
데옥시라이보즈핵산
에치노마이신
구조
동역학
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