Nat commun: scientists use small molecules to change the three-dimensional structure of DNA, which is expected to develop new anticancer drugs

April 28, 2019 / BIOON / - researchers found that small molecular compounds can change the spatial structure of genome, which are considered to be promising anticancer drugs This work has opened up a new direction for the development of a new class of anticancer epigenetic drugs that can change the three-dimensional genome The research results are published in the journal Nature communications Photo source: the characteristics of nature communications organisms are encoded in their genomes In most cases, the physical carrier of genomes is DNA Although DNA is a linear molecule, it is folded in the nucleus, which means that genes and distant regulatory elements may coexist in physical space, forming a complex regulatory network The special mechanism that controls the function of human genes operates at the level of DNA packaging These mechanisms are exactly what this study is interested in In this study, scientists demonstrated for the first time that the three-dimensional structure of the genome can be changed by small molecules that can penetrate living cells Arrow toxin is a kind of compounds with anticancer activity They can kill cancer cells and inhibit the development of cancer Professor Katerina gurova's Laboratory (Roswell Park Comprehensive Cancer Center) has previously demonstrated that arrow toxin can specifically kill cancer cells A drug developed by the research group is currently undergoing phase 1 clinical trials "We used a compound from the arrow toxin family It can combine with DNA and change its physical properties, so that important protein factors that maintain the spatial structure of genome can be separated from DNA This led to significant changes in the three-dimensional genome, which inhibited many genes, mainly oncogenes " Professor Sergey Razin, head of the study and head of the Department of functional genomics, Institute of genetic biology, Russian Academy of Sciences, said Omar kantidze, one of the authors of the paper and head of the genomic stability Laboratory of the Institute of genetic biology, Russian Academy of Sciences, added: "this study may stimulate the study of new drugs that change gene expression by changing spatial genomic tissue." Looking for so-called epigenetic drugs has become a hot research trend However, there are no small molecules that directly affect the three-dimensional genome The results of this work provide a new method for the development of epigenetic drugs Reference: Omar L kantidze et al, the anti cancer drugs curaxes target spatial general organization, nature communications (2019) Doi: 10.1038/s41467-019-09500-7