A comparative study of the base pairing properties of oligodeoxynucleotides containing 5-substituted...

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" A comparative study of the base pairing properties of oligodeoxynucleotides containing 5-substituted-2'-deoxyuridines "
M. Ahmadian

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	1112840
Doc. No	:	TLpq304414656
Main Entry	:	M. Ahmadian
Title & Author	:	A comparative study of the base pairing properties of oligodeoxynucleotides containing 5-substituted-2'-deoxyuridines\ M. Ahmadian
College	:	Purdue University
Date	:	1997
student score	:	1997
Degree	:	Ph.D.
Page No	:	185
Abstract	:	Two series of modified dodecamer oligonucleotides were synthesized. The first contained the -C=CCH2R linker at C5 of deoxyuridine at position 4 (T) of 5-d(CGCTAATTAGCG)-3 and the second contained the -SR linker. The goal of the study was to evaluate and compare these two types of side-chains for suitablity as tethers for linking reporter groups to oligonucleotides. Our primary concern was how these tethers would affect duplex stability. The modified nucleosides were synthesized by palladium mediated coupling reactions between the substituted alkyne and 5-(4,4-dimethoxytrityl)-5-iodo-2usd \sp\primeusd-deoxyuridine and between a disulfide and 5-chloromercurio-2-deoxyuridine. The C5 deoxyuridine side chains evaluated included Cusd\equivusdCCH3, Cusd\equivusdCCH2NHC(O)CH3, Cusd\equivusdCCH2N(CH3)\sb2, Cusd\equivusdCCH2NHC(O)C5H4N, Cusd\equivusdCCH2NHC(O)CH, SCH3, SC6H5, and SCH2CH2NHC(O)CH3. The nucleosides containing these substituents were incorporated into oligodeoxyribonucleosides by standard phosphoramidite methodology. Melting studies demonstrated that the sequence containing the Cusd\equivusdCCH3 side chain had the highest usdT\sb{m}usd (60.0C) in comparison to the control sequence usd(T\sb{m}usd 55.9C), and that any additional substituent on C3 of the propynyl group lowered the usdT\sb{m}usd relative to propynyl. Nevertheless, even the most destabilizing substituent, adamantylcarbamoyl, yielded an oligodeoxyribonucleotide that melted at a usdT\sb{m}usd (55.4C) within 0.5C of the control sequence. In contrast the thioether substituents led to lower usdT\sb{m}usd's ranging from 46.4C for SPh to 53.3C for SCH3. However, the oligonucleotide containing the thioether substituent, SCH2CH2NHC(O)CH3 usd(T\sb{m}usd = 52.5C) melted with higher cooperativity than any of the sequences tested and was shown to have the largest negative free energy of formation usd\rm (G\sb{25\sp\circ} = {-}14.1).usd
Subject	:	Biological sciences
	:	Molecular biology
	:	Organic chemistry
	:	Pure sciences