Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice.

Interpretation of X-ray Powder Diffraction Patterns . By H. Lipson and H. Steeple. Pp. viii + 335 + 3 plates. (Mac-millan: London; St Martins Press: New York, May 1970.) £4.

X-Ray Diffraction

DNA is the molecular target for many of the drugs that are used in cancer therapeutics, and is viewed as a non-specific target of cytotoxic agents. Although this is true for traditional chemotherapeutics, other agents that were discovered more recently have shown enhanced efficacy. Furthermore, a new generation of agents that target DNA-associated processes are anticipated to be far more specific and effective. How have these agents evolved, and what are their molecular targets?

https://faculty.missouri.edu/~gatesk/DNAasaTarget.pdf

DNA and its associated processes as targets for cancer therapy

Homopyrimidine oligodeoxyribonucleotides with EDTA-Fe attached at a single position bind the corresponding homopyrimidine-homopurine tracts within large double-stranded DNA by triple helix formation and cleave at that site. Oligonucleotides with EDTA.Fe at the 5' end cause a sequence specific double strand break. The location and asymmetry of the cleavage pattern reveal that the homopyrimidine-EDTA probes bind in the major groove parallel to the homopurine strand of Watson-Crick double helical DNA. The sequence-specific recognition of double helical DNA by homopyrimidine probes is sensitive to single base mismatches. Homopyrimidine probes equipped with DNA cleaving moieties could be useful tools for mapping chromosomes.

/pdf/sequence-specific-cleavage-of-double-helical-dna-by-triple-22e9x05kiy.pdf

Sequence-specific cleavage of double helical DNA by triple helix formation

This article gives a very brief overview of the antibiotic era, beginning from the discovery of first antibiotics until the present day situation, which is marred by the emergence of hard-to-treat multiple antibiotic-resistant infections. The ways of responding to the antibiotic resistance challenges such as the development of novel strategies in the search for new antimicrobials, designing more effective preventive measures and, importantly, better understanding the ecology of antibiotics and antibiotic resistance are discussed. The expansion of conceptual frameworks based on recent developments in the field of antimicrobials, antibiotic resistance, and chemotherapy is also discussed.

/pdf/a-brief-history-of-the-antibiotic-era-lessons-learned-and-2m0depeww8.pdf

A brief history of the antibiotic era: lessons learned and challenges for the future.

Recent advances in understanding how actinomycin binds to DNA have suggested its mechanism of action. Actinomycin binds to a premelted DNA conformation present within the transcriptional complex. This immobilizes the complex, interfering with the elongation of growing RNA chains. The model has a number of implications for understanding RNA synthesis.

https://www.pnas.org/content/pnas/82/16/5328.full.pdf

Actinomycin and DNA transcription

Stereochemistry of actinomycin binding to DNA: II. Detailed molecular model of actinomycin-DNA complex and its implications

Visualization of drug-nucleic acid interactions at atomic resolution. III. Unifying structural concepts in understanding drug-DNA interactions and their broader implications in understanding protein-DNA interactions.

Visualization of drug-nucleic acid interactions at atomic resolution. I. Structure of an ethidium/dinucleoside monophosphate crystalline complex, ethidium:5-iodouridylyl (3'-5') adenosine.

The three dimensional structure of a crystalline complex containing actino-mycin D and deoxyguanosine has shed light on the stereochemistry of actino-mycin binding to DNA. The phenoxa-zone ring system of actinomycin intercalates into the DNA helix, while deoxyguanosine residues interact with both cyclic peptides through specific hydrogen bonds.

Henry M. Sobell

Papers

Actinomycin and DNA transcription

Stereochemistry of actinomycin binding to DNA: II. Detailed molecular model of actinomycin-DNA complex and its implications

Visualization of drug-nucleic acid interactions at atomic resolution. III. Unifying structural concepts in understanding drug-DNA interactions and their broader implications in understanding protein-DNA interactions.

Visualization of drug-nucleic acid interactions at atomic resolution. I. Structure of an ethidium/dinucleoside monophosphate crystalline complex, ethidium:5-iodouridylyl (3'-5') adenosine.

Stereochemistry of actinomycin--DNA binding.