Efforts toward Expansion of the Genetic Alphabet: Optimization of Interbase Hydrophobic Interactions

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• 作者：Yiqin Wu ; Anthony K. Ogawa ; Markus Berger ; Dustin L. McMinn ; Peter G. Schultz ; and Floyd E. Romesberg
• 刊名：Journal of the American Chemical Society
• 出版年：2000
• 出版时间：August 16, 2000
• 年：2000
• 卷：122
• 期：32
• 页码：7621 - 7632
• 全文大小：169K
• 年卷期：v.122,no.32(August 16, 2000)
• ISSN：1520-5126

文摘

Six novel unnatural nucleobases have been characterized that form stable base pairs in duplex DNA,relying not on hydrogen bonds, but rather on interbase hydrophobic interactions. These nucleobases arederivatives of the hydrophobic base pair between 7-azaindole (7AI) and isocarbostyril (ICS). Derivatives of7AI and ICS were examined that have increased hydrophobic surface area, as well as increased polarizability.As observed with 7AI and ICS, these derivatives are recognized as substrates by Klenow fragment of Escherichiacoli DNA polymerase I. The unnatural base pair between pyrrolopyrizine (PP) and C3-methylisocarbostyril(MICS) is enzymatically incorporated into DNA with high efficiency (k_cat/K_M = 10⁶ M^-1 min^-1) and moderateselectivity. These studies represent a significant step toward the generation of a stable, orthogonal base pairthat can be enzymatically incorporated into DNA with good fidelity.