Recognition and regulation of unique nucleic acid structures by small molecules

Abstract

DNA and RNA are both polymorphic. Depending on the sequences and environmental conditions, they could exist in a variety of secondary structures that play key roles in many biological processes. Recognition of these structures by small ligands is very important for the development of new drugs and new tools. In this article, we will focus on recent advances in the field of molecular recognition and regulation of small ligands with several unique nucleic acid structures, and we will also highlight some of their potential applications in medicinal chemistry and biotechnology.

A pyrene-imidazolium derivative that selectively Recognizes G-Quadruplex DNA

“…Recent studies show that this unique structure can be formed not only in the telomeric region of the genome, but also among other guanine rich sequences having the potential to form quadruplex elsewhere in the human genome [8,9]. Efficient detection of G-quadruplex in addition to stabilization of the G-quadruplex structure is very helpful in designing cancer drugs and in diagnosis of various diseases [10,11]. Detection method taking advantage of fluorescence is so much simple and sensitive [12e15] that there have been reports on fluorophore labelled G-quadruplex oligonucleotide [16e18] or label free probe systems for sensing G-quardruplex [19e23].…”

Supramolecular Chirality in Dynamic Coordination Chemistry

“…The classic example of the F1 motor in ATP synthase shows that supramolecular chirality can regulate the rotational direction of protein motors to maintain homeostasis [5,6]. Helicity switching between a right-handed B-DNA helix and a left-handed Z-DNA may be involved in regulating gene expression and in DNA processing events [6,7].…”

Targeting Nucleic Acids using Dynamic Combinatorial Chemistry

“…[5][6][7][8][9][10][11] Medicinal and synthetic chemists have incorporated the features present in natural products to design new ligands in order to elucidate the rules that govern nucleic acid recognition. [5,12,13] While significant progress has been made in the design of synthetic molecules that bind to the minor groove of DNA, [12] the design of sequence-specific compounds that bind to the major or minor grooves remains challenging. Similarly, while good progress has been made in the design of synthetic ligands that stabilize triplex and quadruplex DNA, [9,[14][15][16] an improved understanding of how to target the unique molecular recognition features of different DNA secondary structures is still required.…”

“…[1][2][3] The flexibility of these biomolecules leads to a diversity of secondary structures, whose formation and stability is highly dependent on the base sequence and environment. [4,5] The study of small molecules that recognize and bind with high affinity and selectivity to duplex, triplex, and quadruplex DNA, as well as hairpins, bulges, and RNA loops has attracted significant interest because of the involvement of many of these structures in disease. [5][6][7][8][9][10][11] Medicinal and synthetic chemists have incorporated the features present in natural products to design new ligands in order to elucidate the rules that govern nucleic acid recognition.…”

“…[4,5] The study of small molecules that recognize and bind with high affinity and selectivity to duplex, triplex, and quadruplex DNA, as well as hairpins, bulges, and RNA loops has attracted significant interest because of the involvement of many of these structures in disease. [5][6][7][8][9][10][11] Medicinal and synthetic chemists have incorporated the features present in natural products to design new ligands in order to elucidate the rules that govern nucleic acid recognition. [5,12,13] While significant progress has been made in the design of synthetic molecules that bind to the minor groove of DNA, [12] the design of sequence-specific compounds that bind to the major or minor grooves remains challenging.…”