NMR studies of echinomycin binding to $[d(CGTACG)]_2$ and $[d(ACGTATACGT)]_2$ : conformational changes between echinomycin binding sitesEchinomycin 과 결합한 [d(CGTACG)]2와 [d(ACGTATACGT)]2에 관한

The complexes formed between the cyclic octadepsipeptide antibiotic echinomycin and the hexamer [d(CGTACG)]$_2$ and decamer [d(ACGTATACGT)]$_2$ have been investigated by using one and two dimensional proton NMR spectroscopy techniques. The results obtained for the two complexes are compared to each other, to the crystal structures of related DNA-echinomycin complexes, and to enzymatic and chemical footprinting results. According to the crystal structure of echinomycin with the hexamer [d(CGTACG)]$_2$, two echinomycins bind to each DNA duplex with the quinoxaline rings bracketing the CpG steps and the central A-T base pairs are Hoogsteen base paired. We have used a new synthetic methodology which involves specific deuterium labeling of the DNA oligomer to identify this Hoogsteen base pair feature with NOE. Through NOE experiment at low temperature (1$^\circ$C), A-T Hoogsteen base pairs in [d(CGTACG]$_2$-echinomycin complex have been identified in solution state. Based on the results of NOESY, the terminal A-T base pairs of the [d(ACGTATACGT)]$_2$ complex have been shown to be Hoogsteen base paried, but none of the four central A-T base pairs were Hoogsteen base paried. All four central A-T base paris were destabilized relative to those in free DNA. According to these and other results, we conclude that the formation of stable Hoogsteen base paris may not be the relevant structural change in vivo. The structural changes propagated between adjacent ACGT binding sites are the unwinding of the duplex and destabilization of the base pairing between binding sites.
Advisors
Choi, Byong-Seok (최병석)researcher
Publisher
한국과학기술원
Issue Date
1993
Identifier
68363/325007 / 000911276
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 화학과, 1993.2, [ iv, 45 p. ]

URI
http://hdl.handle.net/10203/32633
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=68363&flag=t
Appears in Collection
CH-Theses_Master(석사논문)
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