Amirhossein Taghavi

• PhD Student at University of Luxembourg

RNA is a key drug target that can be modulated by small molecules, however covalent binders of RNA remain largely unexplored. Using a high-throughput mass spectrometry screen of 2,000 electrophilic compounds, we identified ligands that react with RNA in a binding-dependent manner. RNA reactivity was influenced by both the reactive group and the RNA...

Hits identified from screening diverse compound libraries against RNA targets can be used to inform design of RNA-focused libraries via computational techniques to calculate chemical similarity and physicochemical properties.

Although glycosidic bonds in purines typically involve the N9 position, the chemical synthesis of adenosine produces N7-ribofuranosyladenine (7A) as a kinetically favorable ribosylation product. Similarly, in the synthesis of LNA-adenosine (AL), a minor product, N7-LNA-adenosine (7AL), is observed. While extensive research has focused on investigat...

RNA repeat expansions fold into stable structures and cause microsatellite diseases such as Huntington’s disease (HD), myotonic dystrophy type 1 (DM1), and spinocerebellar ataxias (SCAs). The trinucleotide expansion of r(CAG), or r(CAG) exp , causes both HD and SCA3, and the RNA’s toxicity has been traced to its translation into polyglutamine (poly...

Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington’s disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to the structured RNAs. Both Huntington’s disease-like 2 (HDL2) and my...

Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington's disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to the structured RNAs. Both Huntington's disease-like 2 (HDL2) and my...

RNA has a broad range of roles in cellular processes, including regulation of gene expression, translation, and formation of molecular machinery. Its implication in disease progression makes RNA a precious target for treating currently untreatable disorders. Modified RNA residues offer unique properties that can be utilized to control binding affin...

Myotonic dystrophy type 1 (DM1) is caused by a highly structured RNA repeat expansion, r(CUG)exp, harbored in the 3' untranslated region (3' UTR) of dystrophia myotonica protein kinase (DMPK) mRNA and drives disease through a gain-of-function mechanism. A panel of low-molecular-weight fragments capable of reacting with RNA upon UV irradiation was s...

G4C2 and G2C4 repeat expansions in chromosome 9 open reading frame 72 (C9orf72) are the most common cause of genetically defined amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), or c9ALS/FTD. The gene is bidirectionally transcribed, producing G4C2 repeats [r(G4C2)exp] and G2C4 repeats [r(G2C4)exp]. The c9ALS/FTD repeat expansi...

Although fragment-based drug discovery (FBDD) has been successfully implemented and well-explored for protein targets, its feasibility for RNA targets is emerging. Despite the challenges associated with the selective targeting of RNA, efforts to integrate known methods of RNA binder discovery with fragment-based approaches have been fruitful, as a...

Although fragment-based drug discovery (FBDD) has been successfully implemented and well-explored for protein targets, its feasibility for RNA targets is emerging. Despite the challenges associate with the selective targeting of RNA, efforts to integrate known methods of RNA binder discovery with fragment-based approaches has been fruitful, as a fe...

RNA G4C2 and C4G2 repeat expansions in the chromosome 9 open reading frame 72 gene (C9orf72) are the most common cause of genetically defined amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), referred to as c9ALS/FTD. The gene is bidirectionally transcribed, producing G4C2 repeats, r(G4C2)exp, in the sense and C4G2 repeats, r(C...

In order to improve the accuracy of molecular dynamics simulations, classical forcefields are supplemented with a kernel-based machine learning method trained on quantum-mechanical fragment energies. As an example application, a potential-energy surface is generalized for a small DNA duplex, taking into account explicit solvation and long-range ele...

In order to improve the accuracy of molecular dynamics simulations, classical force fields are supplemented with a kernel-based machine learning method trained on quantum-mechanical fragment energies. As an example application, a potential-energy surface is generalised for a small DNA duplex, taking into account explicit solvation and long-range el...

DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase – CORRIGENDUM - Volume 51 - Amirhossein Taghavi, Paul van der Schoot, Joshua T. Berryman

Using atomistic simulations, we show the formation of stable triplet structure when particular GC-rich DNA duplexes are extended in solution over a timescale of hundreds of nanoseconds, in the presence of organic salt. We present planar-stacked triplet disproportionated DNA (Σ DNA) as a possible solution phase of the double helix under tension, sub...