The discovery of the DNA double helix, or the revolution that ushered in the era of molecular biology (Nobel Prize 1962)

The 1950s were marked by groundbreaking discoveries in the research of the molecular structure of DNA. The chronology of awarding Nobel Prizes to the authors of these discoveries, did not always coincide with the chronology of announcing the results of their research. J. Watson and F. Crick published their short paper on the discovery of DNA structure, which rocked the scientific world, in Nature in 1953, but received the Nobel Prize together with M. Wilkins only 9 years later. The discovery of the DNA chemical structure is recognized as one of the greatest biological discoveries of the twentieth century. This landmark scientific breakthrough began the development of a new field of the life sciences: molecular biology

The discovery of genetic control of enzyme and virus synthesis: 1965 Nobel Prize Laureates André Lwoff, François Jacob, Jacques Monod

The middle of the 20th century was marked by a number of significant events in molecular biology, among which the groundbreaking discovery of the double helix of DNA, which could self-replicate and thus perform the main life function; the isolation of enzymes for DNA synthesis, and DNA synthesis outside the cell, to name but a few. However, the question of how the information transmission from DNA to proteins is regulated remained open. The concept of the mechanism of regulation of prokaryotic gene activity developed by three French scientists (André Lwoff, François Jacob, Jacques Monod; Nobel Prize 1965), which was a logical outcome of the research in genetics and biochemistry over the previous decades, is recognized to be one of the remarkable achievements in molecular biology. This article describes the essence of the discovery of Lwoff, Jacob and Mono that is the identification of two different groups of genes – structural and functional – and the role that these genes perform in the transmission of genetic information

The discovery of the mechanisms of biological synthesis of nucleic acids: 1959 Nobel laureates S. Ochoa and A. Kornberg

Alongside the chemical and physical research of nucleic acids in the 1940s-50s, the mechanisms of their biosynthesis were investigated. Thus, in 1959, Severo Ochoa and Arthur Kornberg were awarded the Nobel Prize in Physiology or Medicine for the discovery of the mechanisms of biological synthesis of RNA and DNA. The experiments performed by Ochoa and Kornberg are considered today the cornerstone of genetic engineering, as they first demonstrated the possibility of synthesizing RNA and DNA outside the living cell, and also as the enzymes they discovered were among the first tools of this technology

Breaking the genetic code – a new revolutionary stage in the development of molecular biology: 1968 Nobel Prize laureates M. W. Nirenberg, H. G. Khorana, R. W. Holley

This review presents the life stories of M. Nirenberg, H. Khorana, and R. Holley, winners of the 1968 Nobel Prize in Physiology or Medicine, the history of the discoveries made by these scientists, and the methodological approaches used in their works. Owing to the M. Nirenberg and H. Khorana research, the nucleotide compositions of all mRNA triplet codons were decoded. H. Khorana was the first scientist to experimentally prove the direct link between the nucleotide sequence of DNA and the amino acid sequence of the synthesized protein and to obtain a synthetic gene. R. Holley was the first to completely decode the sequence of transport RNA, determine its secondary structure and role in protein synthesis on the ribosome. The Nobel Prize awarded to the scientists was a recognition of their contribution in understanding the mechanisms of coding and reading genetic information and marked a breakthrough moment in the development of molecular biology

Activation of store – operated Ca(2+) entry in cisplatin resistant leukemic cells after treatment with photoexcited fullerene C(60) and cisplatin

Ca2+-regulating system in cancer cells is suggested to be remodulated particularly by reduced store-operated Ca2+ entry (SOCE) through plasma membrane in order to maintain moderately reduced cytosolic Ca2+ concentration and to avoid apoptosis. The endoplasmic reticulum (ER) Ca2+ pool content and the size of SOCE in leukemic wild type (L1210) and resistant to cisplatin (L1210R) cells in control, after treatment with either cisplatin (1 µg/ml) or photoexcited fulleren C60 (10-5 M) alone, or their combination were estimated with the use of Indo-1 AM. The SOCE in resistant to cisplatin L1210R cells was found to be lower than in the wild-type cells. After treatment with cisplatin the decrease of thapsigargin (TG)-sensitive ER Ca2+ pool with no significant increase of SOCE was observed in L1210 cells, while no changes were detected in L1210R cells. Photoexcitation of intracellular accumulated fullerene C60 in the visible range of spectrum (410-700 nm) was accompanied by increase of SOCE not only in sensitive, but in resistant cells as well. In resistant L1210R cells treated with photoexcited C60 essential effect of cisplatin on Ca2+ homeostasis became obvious: the size of SOCE proved to be higher than after treatment with photoexcited C60 alone. The data obtained allow suggesting­ the influence of photoexcited C60 not only on Ca2+-regulating system, but on those involved in controlling cisplatin entry into drug resistant cancer cells

C₆₀ fullerene as synergistic agent in tumor-inhibitory doxorubicin treatment

Background Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C60 fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Do

C₆₀ fullerene as synergistic agent in tumor-inhibitory doxorubicin treatment

Background Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C60 fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Do

Computer prediction of biological activity of dimethyl-N-(benzoyl)amidophosphate and dimethyl-N-(phenylsulfonyl)amidophosphate, evaluation of their cytotoxic activity against leukemia cells in vitro

Structural analogues of β-diketones – dimethyl-N-(benzoyl)amidophosphate (HCP) and dimethyl-N-(phenylsulfonyl)amidophosphate (HSP) were synthesized and identified by the methods of IR, 1H and 31P NMR spectroscopy. Screening of biological activity and calculation of physicochemical parameters of HCP and HSP compounds were done with the use of PASS and ACD/Labs computer programs. A wide range of biological activity of synthesized compounds, antitumor activity in particular, has been found. Calculations of the bioavailability criteria indicate that the investigated compounds have no deviations from Lipinski’s rules. HCP compound is characterized by a high lipophilicity at physiological pH as compared to HSP. It was found that cytotoxic effect of the studied compounds on the leukemiс L1210 cells was of time- and dose-dependent character. HCP is characterized by more pronounced and early cytotoxic effects as compared to HSP. It was shown that 2.5 mM HCP increased ROS production 3 times in the early period of incubation, and decreased cell viability by 40% after 48 h, and by 66% – after 72 h. Based on the computer calculation and undertaken research, HCP was selected for target chemical modifications and enhancement of its antitumor effect