Abstract
Development of valid structure–activity relationships (SARs) is a key to the elucidation of pathomechanisms of epigenetic diseases and the development of efficient, new drugs. The present review is based on selected methodologies and applications supplying molecular structure, binding affinity and biological activity data for the development of new SARs. An emphasis is placed on emerging trends and permanent challenges of new discoveries of SARs in the context of proteins as epigenetic drug targets. The review gives a brief overview and classification of the molecular background of epigenetic changes, and surveys both experimental and theoretical approaches in the field. Besides the results of sophisticated, cutting edge techniques such as cryo-electron microscopy, protein crystallography, and isothermal titration calorimetry, examples of frequently used assays and fast screening techniques are also selected. The review features how different experimental methods and theoretical approaches complement each other and result in valid SARs of the epigenome.
Highlights
According to Waddington, epigenetics is “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being” [1,2]
The PTMs of the H3K4 residue is recognized by fourteen different reader proteins [40], including plant homeodomain (PHD) finger containing proteins, recombination activating gene protein 2 (RAG2), inhibitor of growth protein 2 (ING2), bromodomain PHD finger transcription factor (BPTF), AIRE, Tudor domain containing protein, SAGA complex associated factor 29 (Sgf29) and chromo domain containing proteins Jumonji domain containing 2A (JMJD2A) and chromodomain helicase DNA-binding (CHD) [129,130]
The xenograft tests are applied in tumor growth studies in vivo, where cancer cell lines are transferred into animals, control and treated groups are formed to study the effect of a drug on tumor size
Summary
According to Waddington, epigenetics is “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being” [1,2]. Histone acetylation plays an important role in regulating gene activity, through influencing the stability of the chromatin [36] and is important in diabetes, asthma, and cancer [24,56]. A decreased miR-29 expression leads to an increase in the activity of DNMT3A and DNMT3B [24], both mechanisms result in tumor suppressor gene silencing These methyltransferases are frequently up-regulated in lung cancer, and associated with poor prognosis [60]. Not every gene contains an ERE sequence that is regulated by ERs, which necessitates distinct modes of endocrine action They can modulate the function of other transcription factors, through protein–protein interactions, as non-genomic actions, orphan nuclear hormone receptor SF-1, can serve as a direct binding site for hERα, but not hERβ [64]. The Sections survey recent approaches and selected contributions to the development of structure–activity relationships (SARs) of the epigenome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
