Current Organic Chemistry - Volume 4, Issue 9, 2000

The ubiquitous and essential nature of DNA predicts that enzymes responsible for DNA synthesis evolved early and share a common design and mechanism of action. DNA polymerases from many different organisms do exhibit striking similarities in their overall architecture, the design of the catalytic site, and the mechanism of nucleotidyl transfer. In spite of these shared features, however, DNA polymerases display an astonishing variety in structure and function, ranging The ubiquitous and essential nature of DNA predicts that enzymes responsible for DNA synthesis evolved early and share a common design and mechanism of action. DNA polymerases from many different organisms do exhibit striking similarities in their overall architecture, the design of the catalytic site, and the mechanism of nucleotidyl transfer. In spite of these shared features, however, DNA polymerases display an astonishing variety in structure and function, ranging

The interactions of small molecules with nucleic acids have provoked considerable interest in the field of anticancer drug design over the past three decades; however, critical information linking the physical-chemical properties associated with these complexes with their biological effectiveness remains unclear. Significant progress has been made towards unraveling the structural and dynamic properties of many ligand-DNA complexes which has provided pivotal insight into the design and development of more effective second and third generation chemotherapeutic agents for the successful treatment of many types of cancer. Interactions of ligands with DNA are studied by a variety of physical and biochemical methods in an effort to determine the chemical and physical basis of novel binding phenomena such as DNA base sequence selectivity, correlation of structure-activity relationships, linkages between the geometry and thermodynamic properties describing drug-DNA complexes, and influences of substituent modifications on the physical, chemical, and biological properties of the drug-DNA complex.

Peptide Nucleic Acids (PNA) invented ten years ago are emerging rapidly as useful molecules in DNA hybridization and antisense techniques. Although therapeutic drugs based on PNA are still not in sight, applications in diagnostics, in particular in situ hybridization and PCR based systems, are making rapid strides. The simple structure of PNA in combination with impressive DNA mimicking properties has already provided inspiration to many synthetic organic chemists for designing and preparing several derivatives and analogs towards improving their physico-chemical and biological properties. This review which is not intended to be exhaustive, is aimed at highlighting the current progress in the areas of PNA chemistry, structure, hybridization, and applications. The various chemical backbone modifications of PNA reported till date are summarized in the context of DNA hybridization properties.

The development of high throughput techniques, such as DNA microarrays, engages interest in many biomedical research fields. They are becoming one of the preferred methods for large-scale expression analyses. The power of this technology is that it allows the profiling of thousands of genes in one single experiment. There are two main array-based technologies: cDNA and oligonucleotide arrays hundreds to thousands of immobilized DNA probes, which are hybridized to fluorescent or radioactive complementary cDNA obtained from a target sample. Oligonucleotide chips differ in that probes are 20-25 mer selected oligonucleotides, which are bound to glass substrates and that the DNA obtained from a target sample can only be fluorescently labeled. In this review, we describe the different types of DNA-chips, the steps involved in the production of microchips, the methodological and technical aspects of microchip utilization, and their potential applications including some practical considerations utilizing clinical material.