Catalytic Nucleic Acids: Biochemistry, Chemical Biology, Biosensors, and Nanotechnology

Abstract

Since the initial discovery of ribozymes in the early 1980s, catalytic nucleic acids have been used in different areas. Compared with protein enzymes, catalytic nucleic acids are programmable in structure, easy to modify, and more stable especially for DNA. We take a historic view to summarize a few main interdisciplinary areas of research on nucleic acid enzymes that may have broader impacts. Early efforts on ribozymes in the 1980s have broken the notion that all enzymes are proteins, supplying new evidence for the RNA world hypothesis. In 1994, the first catalytic DNA (DNAzyme) was reported. Since 2000, the biosensor applications of DNAzymes have emerged and DNAzymes are particularly useful for detecting metal ions, a challenging task for enzymes and antibodies. Combined with nanotechnology, DNAzymes are key building elements for switches allowing dynamic control of materials assembly. The search for new DNAzymes and ribozymes is facilitated by developments in DNA sequencing and computational algorithms, further broadening our fundamental understanding of their biochemistry.

The noncovalent dimerization of a G-quadruplex/hemin DNAzyme improves its biocatalytic properties

“…Besides its function as the repository of genetic information, DNA molecules are increasingly studied for their biocatalytic properties, oen referred to as DNAzymes. [1][2][3][4][5][6][7][8][9][10][11] Catalytic DNA usually comprises a sequence in which a tertiary structure is encoded which, upon interaction with a metal cofactor, 12 accelerates chemical reactions. [13][14][15][16][17][18][19][20][21] An interesting tertiary structure is the G-quadruplex (GQ) that folds from guanine-rich sequences through the stacking of G-quartets, i.e., arrays of four guanines associated via Hoogsteen hydrogen bonds.…”

Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes

“…225 The largest and most diverse field of applications is found in bio-and nanotechnology, where DNAzymes are used as components of analytical devices for biosensors and logic gates. [226][227][228] Recent reviews summarize diverse metal ion-dependent transesterification DNA enzymes and their applications. [228][229][230] In many analytical applications, the substrate is a DNA strand with a single ribonucleotide incorporated, linked to a FRET pair, with donor and acceptor placed before and after the cleavage site.…”

“…[226][227][228] Recent reviews summarize diverse metal ion-dependent transesterification DNA enzymes and their applications. [228][229][230] In many analytical applications, the substrate is a DNA strand with a single ribonucleotide incorporated, linked to a FRET pair, with donor and acceptor placed before and after the cleavage site. 231 A DNA sequence with a single ribonucleotide was also used as a substrate for in vitro selections that aimed at generalizing the substrate sequence tolerance at the cleavage site.…”

Intersecting Xenobiology and Neometabolism To Bring Novel Chemistries to Life

“…Xenonucleic acids (XNAs) are genetic polymers with backbone structures different from those associated to DNA and RNA. [163] Similarly, XNAzymes are the xeno analogues of ribozymes and DNAzymes [164] -folded polymers build of unnatural nucleic acid units able to catalyze a certain reaction. Currently, the number of XNAzymes is limited, but, interestingly, one of them is the group of 2'-fluoroarabino nucleic acid enzymes or FANAzymes.…”