A5055861650- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- DNA and Nucleic Acid Chemistry
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Protein Structure and Dynamics
- vaccines and immunoinformatics approaches
- Advanced NMR Techniques and Applications
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Computational Drug Discovery Methods
- Infectious Encephalopathies and Encephalitis
- COVID-19 Clinical Research Studies
- Crystallography and molecular interactions
- SARS-CoV-2 detection and testing
- RNA Interference and Gene Delivery
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- RNA regulation and disease
- Thermodynamic properties of mixtures
- Molecular spectroscopy and chirality
- Advanced Biosensing Techniques and Applications
- Various Chemistry Research Topics
- Phase Equilibria and Thermodynamics
Goethe University Frankfurt
2009-2025
National Renewable Energy Laboratory
2024
University of Colorado Boulder
2024
Leibniz-Institute for New Materials
2024
Environmental Energy & Engineering
2024
The University of Adelaide
2024
Imperial College London
2024
Robert Bosch (Germany)
2023
Goethe Institute
2007
Georg Speyer Haus
2006
Abstract The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights need for coordinated research to combat COVID-19. A particularly important aspect is development of medication. In addition viral proteins, structured RNA elements represent a potent alternative as drug targets. search drugs that target requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, worldwide consortium NMR researchers aims...
SARS-CoV-2 contains a positive single-stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 elements were identified as conserved between SARS-CoV and SARS-CoV-2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these fold independently, in line with data from vivo ex-vivo structural probing experiments. These contain non-base-paired regions potentially harbor ligand-binding pockets. Here, performed an NMR-based screening poised...
Among the three major classes of biomacromolecules (DNA, RNA, and proteins) RNA's pronounced dynamics are most explicitly linked to its wide variety functions, which include catalysis regulation transcription, translation, splicing. These functions mediated by a range RNA biomachinery, including such varied examples as macromolecular noncoding RNAs, microRNAs, small interfering riboswitch thermometers. In each case, functional an interconversion is characterized associated rate constant....
The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands redirection of scientific efforts criteria organized research projects. international COVID19-NMR consortium seeks provide such new approaches gathering expertise worldwide. In particular, making available viral proteins RNAs will pave way understanding molecular components in detail. resources provided through are fully disclosed accelerate access exploitation. NMR...
We present the high-resolution structure of stem-loop 4 5'-untranslated region (5_SL4) severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) genome solved by solution state nuclear magnetic resonance spectroscopy. 5_SL4 adopts an extended rod-like with a single flexible looped-out nucleotide and two mixed tandem mismatches, each composed G•U wobble base pair pyrimidine•pyrimidine mismatch, which are incorporated into structure. Both mismatches residue destabilize locally. Their...
In a combined NMR/MD study, the temperature-dependent changes in conformation of two members RNA YNMG-tetraloop motif (cUUCGg and uCACGg) have been investigated at temperatures 298, 317 325 K. The considerable different thermal stability biological functions. order to address these differences, study was performed. large temperature range represents challenge for both, NMR relaxation analysis (consistent choice effective bond length CSA parameter) all-atom MD simulation with explicit solvent...
SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The increased vaccines, thus necessitating for development new intervention strategies including anti-virals. Within international Covid19-NMR consortium, we have identified binders targeting RNA genome SCoV2. We established protocols production NMR characterization more than 80 % all SCoV2 proteins. Here, performed an screening using a fragment library binding 25 proteins hits also against...
Targeting the RNA genome of SARS‐CoV‐2 is a viable option for antiviral drug development. We explored three ligand binding sites core pseudoknot frameshift element. iteratively optimized ligands, based on improved affinities, targeting these and report structural dynamic properties identified sites. Available experimental 3D structures element were compared to SAXS NMR data validate its dominant folding state in solution. In order experimentally map silico predicted sites, assignments...
Targeting the RNA genome of SARS‐CoV‐2 is a viable option for antiviral drug development. We explored three ligand binding sites core pseudoknot frameshift element. iteratively optimized ligands, based on improved affinities, targeting these and report structural dynamic properties identified sites. Available experimental 3D structures element were compared to SAXS NMR data validate its dominant folding state in solution. In order experimentally map silico predicted sites, assignments...
The interaction of the nucleocapsid NCp7 human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with RNA packaging signal Psi ensures specific encapsidation dimeric full length viral genome into nascent particles. Being an essential step in HIV-1 replication cycle, represents a promising target for therapeutic intervention. We previously selected peptides binding to Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis peptide variants consensus HWWPWW motif...
Hydrogen bonds involving phosphate groups as acceptors only occur in noncanonical structure elements of RNAs and are important for their stable folding. These hydrogen can be directly assigned by H,P correlation experiments solution NMR spectroscopy owing to the presence sizeable 2hJHP scalar couplings across bond. will provide valuable information speed up determination complex RNA structures. Detailed facts importance specialist readers published ”Supporting Information”. Such documents...
Target TAR by NMR: Tripeptides containing arginines as terminal residues and non-natural amino acids central are good leads for drug design to target the HIV trans-activation response element (TAR). The structural characterization of RNA-ligand complex NMR spectroscopy reveals two specific binding sites that located at bulge residue U23 around pyrimidine-stretch U40-C41-U42 directly adjacent bulge.
The nucleocapsid protein (NC) of HIV-1 exerts critical functions in viral genome replication and virus assembly. Since the recognition target nucleic acids is required initial step most NC-mediated processes, attempts were made to find small molecules capable competing with this recognition. In particular, several Trp-rich hexapeptides recently found strongly bind RNA sequences targeted by NC. To further validate these peptides as potential anti-NC agents, we studied ability Ac-HKWPWW-NH2,...
Tying up the package: The HIV-1 RNA packaging signal ψ is a complex structure located within 5′-end of unspliced RNAs (see picture). Upon binding viral polyprotein Gag to RNA, process mediated by nucleocapsid protein NCp7, two genomes are packaged into assembling virions. By using phage display technology peptides were selected that bind specifically different structures derived from RNA.
Abstract Non‐natural amino acids with aromatic or heteroaromatic side chains were incorporated into tripeptides of the general structure Arg‐X‐Arg and tested as ligands HIV RNA element TAR. Some these compounds could compete efficiently association TAR Tat downregulated a TAR‐controlled reporter gene in HeLa cells. Peptide 7 , which contains 2‐pyrimidinyl‐alkyl chain, also inhibited spread HIV‐1 cell cultures. NMR studies bound to HIV‐2‐TAR gave evidence for contacts bulge region.
Abstract SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The increased vaccines, thus necessitating for development new intervention strategies including anti‐virals. Within international Covid19‐NMR consortium, we have identified binders targeting RNA genome SCoV2. We established protocols production NMR characterization more than 80 % all SCoV2 proteins. Here, performed an screening using a fragment library binding 25 proteins hits also against...
Abstract The outbreak of COVID‐19 in December 2019 required the formation international consortia for a coordinated scientific effort to understand and combat virus. In this Viewpoint Article, we discuss how NMR community has gathered investigate genome proteome SARS‐CoV‐2 tested them binding low‐molecular‐weight binders. External factors including extended lockdowns due global pandemic character viral infection triggered transition from locally focused collaborative research conducted...
Wasserstoffbrücken mit Phosphatgruppen als Akzeptoren treten ausschließlich in nichtkanonischen Strukturelementen von RNAs auf und sind wichtig für deren stabile Faltung. Weil signifikante skalare 2hJHP-Kopplungen über die vorliegen, können diese direkt durch H,P-Korrelationsexperimente der Lösungs-NMR-Spektroskopie nachgewiesen werden. Diese Experimente liefern wertvolle Informationen eine schnellere Bestimmung komplexer RNA-Strukturen.
Abstract SARS‐CoV‐2 contains a positive single‐stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 elements were identified as conserved between SARS‐CoV and SARS‐CoV‐2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these fold independently, in line with data from vivo ex‐vivo structural probing experiments. These contain non‐base‐paired regions potentially harbor ligand‐binding pockets. Here, performed an NMR‐based screening...
Abstract The international Covid19-NMR consortium aims at the comprehensive spectroscopic characterization of SARS-CoV-2 RNA elements and proteins will provide NMR chemical shift assignments molecular components this virus. genome encodes approximately 30 different proteins. Four these are involved in forming viral envelope or packaging therefore called structural other fulfill a variety functions during life cycle comprise so-called non-structural (nsps). Here, we report near-complete...
Abstract The stem-loop (SL1) is the 5'-terminal structural element within single-stranded SARS-CoV-2 RNA genome. It formed by nucleotides 7–33 and consists of two short helical segments interrupted an asymmetric internal loop. This architecture conserved among Betacoronaviruses. SL1 present in genomic as well all subgenomic mRNA species produced virus during replication, thus representing a ubiquitous cis -regulatory with potential functions at stages viral life cycle. We here 1 H, 13 C 15 N...
Exploring the benefits and limits of ligand based combined 1 H 19 F NMR readout for interaction studies viral RNAs with small compounds.