Efforts toward the expansion of the genetic alphabet: Information storage and replication with unnatural hydrophobic base pairs

被引:180
作者
Ogawa, AK [1 ]
Wu, YQ [1 ]
McMinn, DL [1 ]
Liu, JQ [1 ]
Schultz, PG [1 ]
Romesberg, FE [1 ]
机构
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
关键词
D O I
10.1021/ja9940064
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The faithful recognition of the interstrand hydrogen bonds between complementary nucleobases forms the foundation of the genetic code. The ability to replicate DNA containing a stable third base pair would allow for an expansion of the information content of DNA by supplementing the existing two base pairs of the genetic alphabet with a third. We report the optimization of unnatural nucleobases whose pairing in duplex DNA is based on interbase hydrophobic interactions. We show that the stability and selectivity of such unnatural base pairs may be comparable to, or even exceed, that of native pairs. We also demonstrate that several unnatural base pairs are incorporated into DNA by Klenow fragment of Escherichia coli DNA polymerase I with an efficiency equivalent to that of native DNA synthesis. Moreover, the unnatural bases are orthogonal to the native bases, with correct pairing being favored by at least an order of magnitude relative to mispairing.
引用
收藏
页码:3274 / 3287
页数:14
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共 35 条
[21]  
RANDALL SK, 1987, J BIOL CHEM, V262, P6864
[22]   Beyond guanine quartets: cation-induced formation of homogenous and chimeric DNA tetraplexes incorporating iso-guanine and guanine [J].
Roberts, C ;
Chaput, JC ;
Switzer, C .
CHEMISTRY & BIOLOGY, 1997, 4 (12) :899-908
[23]   Theoretical and experimental study of isoguanine and isocytosine: Base pairing in an expanded genetic system [J].
Roberts, C ;
Bandaru, R ;
Switzer, C .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (20) :4640-4649
[24]   2′-deoxyisoguanosine adopts more than one tautomer to form base pairs with thymidine observed by high-resolution crystal structure analysis [J].
Robinson, H ;
Gao, YG ;
Bauer, C ;
Roberts, C ;
Switzer, C ;
Wang, AHJ .
BIOCHEMISTRY, 1998, 37 (31) :10897-10905
[25]   Aromatic nonpolar nucleosides as hydrophobic isosteres of pyrimidine and purine nucleosides (vol 59, pg 7238, 1994) [J].
Schweitzer, BA ;
Kool, ET .
JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (25) :8326-8326
[26]   AROMATIC NONPOLAR NUCLEOSIDES AS HYDROPHOBIC ISOSTERES OF PYRIMIDINE AND PURINE NUCLEOSIDES [J].
SCHWEITZER, BA ;
KOOL, ET .
JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (24) :7238-7242
[27]  
SCHWEITZER BA, 1995, J AM CHEM SOC, V117, P1863, DOI 10.1021/ja00112a001
[28]   SYNTHESIS OF 1,7-DIDEAZA-2'-DEOXYADENOSINE AND RELATED PYRROLO[2,3-B]PYRIDINE 2'-DEOXY-BETA-D-RIBONUCLEOSIDES - STEREOSELECTIVE PHASE-TRANSFER GLYCOSYLATION VIA THE NUCLEOBASE ANION [J].
SEELA, F ;
GUMBIOWSKI, R .
HETEROCYCLES, 1989, 29 (04) :795-805
[29]   Hydrophobicities of the nucleic acid bases: Distribution coefficients from water to cyclohexane [J].
Shih, P ;
Pedersen, LG ;
Gibbs, PR ;
Wolfenden, R .
JOURNAL OF MOLECULAR BIOLOGY, 1998, 280 (03) :421-430
[30]   CHEMICAL SYNTHESIS AND CHARACTERIZATION OF DUPLEX DNA CONTAINING A NEW BASE PAIR - A NONDISRUPTIVE, BENZOFUSED PYRIMIDINE ANALOG [J].
SOLOMON, MS ;
HOPKINS, PB .
JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (08) :2232-2243