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During the past 20 years, polyamides have evolved from the natural product distamycin to a new class of programmable heterocyclic oligomers that bind a broad repertoire of DNA sequences with high affinity and specificity. This chapter details recent advances in this field of research, focusing on molecular recognition of DNA, and biological applications such as modulating gene expression by small...
Competition dialysis is a powerful new tool for the discovery of ligands that bind to nucleic acids with structural- or sequence-selectivity. The method is based on firm thermodynamic principles and is simple to implement. In the competition dialysis experiment, an array of nucleic acid structures and sequences is dialyzed against a common test ligand solution. After equilibration, the amount of ligand...
The cyanine dyes are among the oldest classes of synthetic compounds but continue to find applications in a variety of fields. In many cases, the dyes act as fluorescent labels for biomolecules, and can interact with the biomolecule either through covalent or noncovalent bonding. One particularly important application involves dyes that bind to double helical DNA by intercalation and exhibit large...
Here we explore the subjectivity intrinsic to macromolecular crystallography, focusing on the hydration/counter-ion region of nucleic acids. Water molecules, monovalent and divalent cations, and polyamines compete for similar or adjacent sites. Many of these species give identical electron distributions (electron density maps). Such scattering iso-types allow one to construct different models that...
Cancer chemotherapy relies to a great extent on the use of drugs like doxorubicin, etoposide, and camptothecin derivatives, which are targeted at topoisomerases. These enzymes that resolve DNA topological constraints in cells are the primary targets for a large diversity of natural products extracted from plants, microorganisms or, as reviewed here, from marine organisms. Marine products capable of...
Nucleic acids are polymorphic macromolecules that can adopt a variety of single-, double- and multi-stranded conformations, which in turn may provide important signals for regulating gene expression, and for maintaining genome integrity and stability. The design of tailor-made molecules that recognize specific sequences in the DNA double helix would provide interesting tools to interfere with DNA...
Aminoglycoside antibiotics are bactericidal drugs that have been at the forefront of antimicrobial therapy for almost five decades. The past decade (1990–2000) saw a resurgence in aminoglycoside-based drug development as their chemistry/mechanism of action became better understood. This work, however, had almost exclusively focused on targeting RNA. This review summarizes new developments (past 4–5...
2-Deoxystreptamine (2-DOS) aminoglycosides are a family of structurally related broad-spectrum antibiotics that are used widely in the clinic. Their antibiotic activities are ascribed to their abilities to bind a highly conserved sequence (termed the A site) in the 16S rRNA of the 30S ribosomal subunit and interfere with protein synthesis. The aminoglycosides represent a paradigm for both drug–RNA...
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