Mirror-image RNA that binds D-adenosine

• Published in: Nature biotechnology Vol. 14; no. 9; pp. 1112 - 1115
• Main Authors: Klußmann, Sven, Nolte, Alexis, Bald, Rolf, Erdmann, Volker A, Fürste, Jens P
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01-09-1996
• Subjects: Adenosine - chemistry; Adenosine - metabolism; Analytical, structural and metabolic biochemistry; Base Sequence; Binding Sites; Binding, Competitive; Biological and medical sciences; Biotechnology; Consensus Sequence; Conserved Sequence; DNA - genetics; Drug Stability; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Ligands; Molecular Sequence Data; Nucleic Acid Conformation; Nucleic acids; RNA - chemistry; RNA - genetics; RNA - metabolism; Rna, ribonucleoproteins; Sequence Homology, Nucleic Acid; Stereoisomerism; Stereoisomer; Adenosine; Stability; RNA; Nucleotide sequence; Ligand; Dissociation constant; Homology; Molecular interaction; Stereospecificity; Kinetic parameter
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt0996-1112

A 58-mer L-RNA ligand that binds to naturally occurring D-adenosine with a dissociation constant of 1.7 microM in solution was identified from a combinatorial library employing mirror-design. The corresponding D-RNA ligand shows identical binding affinity to L-adenosine. Reciprocal chiral specificity was also evident from ligand discrimination; the binding affinity of the L-RNA ligand for D-adenosine was 9000-fold greater than its affinity for L-adenosine and vice versa. While the D-RNA ligand was rapidly degraded in human serum, the L-RNA ligand displayed an extraordinary stability. This indicates the potential application of specifically designed L-RNA ligands as stable monoclonal antibody analogues and the development of highly stable L-ribozymes.