Mirror-design of L-oligonucleotide ligands binding to L-arginine

The high affinity and selectivity of nucleic acid ligands have clearly demonstrated that RNA can be targeted to a variety of molecules. In practice, however, the use of unmodified aptamers is impeded by the low stability of RNA in biological fluids. Here we describe the mirror-design of a stable 38-mer L-oligoribonucleotide ligand that binds to L-arginine. This L-RNA ligand was also able to bind to a short peptide containing the basic region of the human immunodeficiency virus type-1 Tat-protein. The L-RNA ligand displayed the expected stability in human serum. These findings may contribute to the identification of novel diagnostics and pharmaceuticals.

[1]  H. Vorbrüggen,et al.  Nucleoside syntheses, XXII1) Nucleoside synthesis with trimethylsilyl triflate and perchlorate as catalysts , 1981 .

[2]  P. Wrede,et al.  Binding oligonucleotides to Escherichia coli and Bacillus stearothermophilus 5 S RNA. , 1978, Journal of molecular biology.

[3]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[4]  E. Recondo,et al.  Eine neue, einfache Synthese des. 1‐O‐Acetyl‐2,3,5‐Tri‐O‐benzoyl‐β‐D‐Ribofuranosides , 1959 .

[5]  A. Riggs,et al.  Lac repressor binding to non-operator DNA: detailed studies and a comparison of eequilibrium and rate competition methods. , 1972, Journal of molecular biology.

[6]  D. Patel,et al.  Solution structure of the donor site of a trans-splicing RNA. , 1996, Structure.

[7]  B. Gaffney,et al.  Transient protection: efficient one-flask syntheses of protected deoxynucleosides , 1982 .

[8]  S. Kent,et al.  Total Chemical Synthesis of a D-Enzyme: The Enantiomers of HIV-1 Protease Show Demonstration of Reciprocal Chiral Substrate Specificity , 1992 .

[9]  G. Knapp Enzymatic approaches to probing of RNA secondary and tertiary structure. , 1989, Methods in enzymology.

[10]  S. Kent,et al.  Total chemical synthesis of a D-enzyme: the enantiomers of HIV-1 protease show reciprocal chiral substrate specificity [corrected]. , 1992, Science.

[11]  M Yarus,et al.  Diversity of oligonucleotide functions. , 1995, Annual review of biochemistry.

[12]  F. Šorm,et al.  Oligonucleotidic compounds. XXXIV. Preparation of some β-L-ribonucleosides, their 2'(3')-phosphates and 2',3'-cyclic phosphates , 1969 .

[13]  N. Janjić,et al.  Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor. , 1995, Chemistry & biology.

[14]  J W Szostak,et al.  In vitro selection of catalytic RNAs. , 1994, Current opinion in structural biology.

[15]  J. Kraut,et al.  A proposed model for interaction of polypeptides with RNA. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[16]  L. Gold,et al.  In vitro selection of RNA ligands to substance P. , 1995, Biochemistry.

[17]  R. Adamiak,et al.  On the Application of t-Butyldimethylsilyl Group in Chemical RNA Synthesis. Part I. 31P NMR Study of 2′-O-t-BDMSi Group Migration During Nucleoside 3′-OH Phosphorylation and Phosphitylation Reactions , 1989 .

[18]  M. Robins,et al.  High-yield regioselective synthesis of 9-glycosyl guanine nucleosides and analogues via coupling with 2-N-acetyl-6-O-diphenylcarbamoylguanine , 1987 .

[19]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[20]  M. Zuker Computer prediction of RNA structure. , 1989, Methods in enzymology.

[21]  C. Betzel,et al.  Crystallization and preliminary diffraction studies of the structural domain E of Thermus flavus 2S rRNA , 1995 .

[22]  Gerald F. Joyce,et al.  Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA , 1990, Nature.

[23]  W. Pfleiderer,et al.  Nucleoside, XXXVII. Synthese und Eigenschaften von 2′‐O‐ und 3′‐O‐(tert‐Butyldi‐methylsilyl)‐5′‐O‐(4‐methoxytrityl)‐ sowie 2′,3′‐Bis‐O‐(tert‐butyl‐dimethylsilyl)ribonucleosiden — Ausgangssubstanzen für Oligoribonucleotid‐Synthesen , 1981 .

[24]  M Yarus,et al.  Three small ribooligonucleotides with specific arginine sites. , 1993, Biochemistry.

[25]  Michael Famulok,et al.  Molecular Recognition of Amino Acids by RNA-Aptamers: An L-Citrulline Binding RNA Motif and Its Evolution into an L-Arginine Binder , 1994 .

[26]  C. Burd,et al.  Conserved structures and diversity of functions of RNA-binding proteins. , 1994, Science.

[27]  Y. Lin,et al.  Modified RNA sequence pools for in vitro selection. , 1994, Nucleic acids research.

[28]  C. Tuerk,et al.  Comprehensive chemical modification interference and nucleotide substitution analysis of an RNA pseudoknot inhibitor to HIV-1 reverse transcriptase. , 1995, Journal of molecular biology.

[29]  A. Holý Nucleic acid components and their analogues. CLIII. Preparation of 2'-deoxy-L-ribonucleosides of the pyrimidine series , 1972 .

[30]  A. Pardi,et al.  High-resolution molecular discrimination by RNA. , 1994, Science.

[31]  C. Vargeese,et al.  Potent 2'-amino-2'-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor. , 1995, Biochemistry.

[32]  阿部 芳廣,et al.  Epimerization of Aldoses Catalyzed by Dioxobis (2, 4-pentanedionato-O, O')-molybdenum (VI). An Improved Procedure for C-2 Epimer Preparation , 1980 .

[33]  V. Erdmann,et al.  Mirror-image RNA that binds D-adenosine , 1996, Nature Biotechnology.

[34]  R. Cedergren,et al.  The automated chemical synthesis of long oligoribuncleotides using 2'-O-silylated ribonucleoside 3'-O-phosphoramidites on a controlled-pore glass support: synthesis of a 43-nucleotide sequence similar to the 3'-half molecule of an Escherichia coli formylmethionine tRNA , 1987 .

[35]  T. Muir A chemical approach to the construction of multimeric protein assemblies. , 1995, Structure.

[36]  P. Schultz,et al.  Expanding the scope of RNA catalysis. , 1994, Science.

[37]  P. Burgstaller,et al.  RNA aptamers that bind L-arginine with sub-micromolar dissociation constants and high enantioselectivity. , 1996, Nucleic acids research.

[38]  A. Holý Nucleic acid components and their analogues. CLV. Mechanism of anomalous opening of the O 2,2' -anhydro bond in uracil cyclonucleosides , 1973 .