A5058448605- Protein Structure and Dynamics
- Advanced Chemical Physics Studies
- Crystallography and molecular interactions
- X-ray Diffraction in Crystallography
- Photochemistry and Electron Transfer Studies
- Crystallization and Solubility Studies
- Chemical Reactions and Mechanisms
- Spectroscopy and Quantum Chemical Studies
- Chemokine receptors and signaling
- Microbial Natural Products and Biosynthesis
- Antimicrobial Peptides and Activities
- Immunotherapy and Immune Responses
- Molecular Spectroscopy and Structure
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Molecular Junctions and Nanostructures
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Fluorine in Organic Chemistry
- 14-3-3 protein interactions
- vaccines and immunoinformatics approaches
- Enzyme Structure and Function
- Radical Photochemical Reactions
- Genetic Neurodegenerative Diseases
- Surface Chemistry and Catalysis
TU Dortmund University
2023-2025
University of California, San Diego
2024
University of Duisburg-Essen
2017-2023
Universidad Nacional Autónoma de México
2023
University of California, Los Angeles
2022
Universität Ulm
2022
University of Michigan
2022
University of Southern California
2022
Max-Planck-Institut für Kohlenforschung
2012-2021
Max Planck Society
2010-2017
SARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of tract against limited, we generated screened peptide/protein library derived from bronchoalveolar lavage for inhibitors spike-driven entry. Analysis antiviral fractions revealed presence α1-antitrypsin (α1AT), highly abundant circulating serine protease inhibitor. Here, report that α1AT inhibits entry at physiological concentrations suppresses viral replication in...
Undecacene, the largest member of acene family, was photogenerated in a polymer matrix under cryogenic conditions from precursor with two α-diketone bridges. The electronic absorption undecacene extends into NIR region, but spectrum is dominated by strong absorptions UV/Vis range. HOMO-LUMO transition continuously shifted to lower energies as number rings increases (E vs. 1/N, N=number rings), which line electron correlation calculated DFT/MRCI.
Virtual screening of protein–protein and protein–peptide interactions is a challenging task that directly impacts the processes hit identification hit-to-lead optimization in drug design projects involving peptide-based pharmaceuticals. Although several tools designed to predict binding affinity complexes have been proposed, methods specifically developed are comparatively scarce. Frequently, predictors trained score small molecules used for peptides indistinctively, despite larger...
Acyltransferase domains control the extender unit recognition in Polyketide Synthases (PKS) and thereby side-chain diversity of resulting natural products. The enzyme engineering strategy presented here allows alteration acyltransferase substrate profile to enable an engineered biosynthesis product derivatives through incorporation a synthetic malonic acid thioester. Experimental sequence-function correlations combined with computational modeling revealed origins these PKS enabled targeted...
Abstract The self-organizational properties of DNA have been used to realize synthetic hosts for protein encapsulation. However, current strategies DNA–protein conjugation still limit true emulation natural host–guest systems, whose formation relies on non-covalent bonds between geometrically matching interfaces. Here we report one the largest complexes semisynthetic origin held in place exclusively by spatially defined supramolecular interactions. Our approach is based decoration inner...
Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides target components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish CLR01, a ‘molecular tweezer’ specific lysine arginine residues, inhibits formation of infectivity-enhancing seminal amyloids remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement infection by virion–amyloid complexes...
The prediction of peptide–protein or protein–protein interactions (PPI) is a challenging task, especially if amino acid sequences are the only information available. Machine learning methods allow us to exploit content in PPI datasets. However, numerical codification these datasets often influences performance data mining approaches. Here, we introduce procedure for general‐purpose polypeptides. This transforms pairs into machine learning‐friendly vector, whose elements represent descriptors...
The three-dimensional structure of a peptide is strongly influenced by its solvent environment. In the present study, we study three cyclic tetrapeptides which serve as model peptides for β-turns. They are general cyclo(Boc-Cys-Pro-X-Cys-OMe) with amino acid X being either glycine (1), or L- D-leucine (L- D-2). Using vibrational circular dichroism (VCD) spectroscopy, confirm previous NMR results showed that D-2 adopts predominantly βII turn in apolar and polar solvents. Our L-2 indicate...
Protein regions that are involved in protein-protein interactions (PPIs) very often display a high degree of intrinsic disorder, which is reduced during the recognition process. A prime example binding rigid 14-3-3 adapter proteins to their numerous partner proteins, whose motifs undergo an extensive disorder-to-order transition. In this context, it highly desirable control entropy-costly process using tailored stabilizing agents. This study reveals how molecular tweezer CLR01 tunes...
Huntington's disease is a neurodegenerative disorder associated with the expansion of polyglutamine tract in exon-1 domain huntingtin protein (htte1). Above threshold 37 glutamine residues, htte1 starts to aggregate nucleation-dependent manner. A 17-residue N-terminal fragment (N17) has been suggested play crucial role modulating aggregation propensity and toxicity htte1. Here we identify N17 as potential target for novel therapeutic intervention using molecular tweezer CLR01. combination...
The interactions between diphenylcarbene DPC and the halogen bond donors CF3I CF3Br were investigated using matrix isolation spectroscopy (IR, UV–vis, EPR) in combination with QM QM/MM calculations. Both CF3X form very strong complexes singlet state of DPC, but only weakly interact triplet DPC. This results a switching spin becoming more stable than complexes. forms second complex (type II) that is thermodynamically slightly stable. Calculations predict this DPC···I distance shorter F3C···I...
Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified endogenous peptide antagonist inverse agonist CXCR4 a promising compound for the development improved analogues therapy CXCR4-associated To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs EPI-X4/CXCR4. Subsequent rational...
Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum infection. Molecular docking enzyme activity assays demonstrate AT binds inhibits TMPRSS2, primes the Spike proteins coronaviruses for subsequent fusion. Consequently, blocks entry driven by Spikes SARS-CoV, MERS-CoV,...
Abstract Activation of the replicative Mcm2-7 helicase by loading GINS and Cdc45 is crucial for replication origin firing, as such faithful genetic inheritance. Our biochemical structural studies demonstrate that activator interacts with TopBP1 through two separate binding surfaces, first involving a stretch highly conserved amino acids in TopBP1-GINI region, second surface on TopBP1-BRCT4. The surfaces bind to opposite ends A domain subunit Psf1. Mutation analysis reveals either...
Selective binding of the phosphate-substituted molecular tweezer 1a to protein lysine residues was suggested explain inhibition certain enzymes and aberrant aggregation amyloid petide Aβ42 or α-synuclein, which are assumed be responsible for Alzheimer's Parkinson's disease, respectively. In this work we systematically investigated four water-soluble tweezers 1a–d (substituted by phosphate, methanephosphonate, sulfate, O-methylenecarboxylate groups) amino acids peptides containing arginine...
This study explores the interactions underlying IR spectra of ionic liquid [NC4111][NTf2] and its deuterated isotopomer [d9-NC4111][NTf2] by first isolating charged building blocks using mass-selective CIVP spectroscopy then following evolution these bands upon sequential assembly constituents. The (1,1) (2,2) neutral ion pairs are recorded superfluid helium droplets as well a solid neon matrix, while those larger aggregates again obtained with CIVP. In general, cluster similar to that bulk,...
While the optical spectra of acene series up to pentacene provide textbook examples for annulation principle, larger members are much less understood. The present work provides an investigation optically allowed excited states from nonacene, largest observed experimentally, using density functional based multireference configuration method (DFT/MRCI). For this purpose, ten lowest energy B2u and B3u irreducible representations were computed. In agreement with previous computational...
In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into toxic assemblies causing β-cell death. Therefore, preventing IAPP toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01 supramolecular tool selective complexation of K residues in (poly)peptides. Surprisingly, it inhibits aggregation at substoichiometric concentrations even though has only one residue position 1, whereas efficient inhibition requires excess CLR01. basis this peculiar...
Interaction mapping is a powerful strategy to elucidate the biological function of protein assemblies and their regulators. Here, we report generation quantitative interaction network, directly linking 14 human proteins AAA+ ATPase p97, an essential hexameric with multiple cellular functions. We show that high-affinity interacting ASPL efficiently promotes p97 hexamer disassembly, resulting in formation stable p97:ASPL heterotetramers. High-resolution structural biochemical studies indicate...
Abstract Photochemical reactions in solution often proceed via competing reaction pathways comprising intermediates that capture a solvent molecule. A disclosure of the underlying mechanisms is challenging due to rapid nature these processes and intricate identification how many molecules are involved. Here combining broadband femtosecond transient absorption quantum mechanics/molecular mechanics simulations, we show for one most reactive species, diphenylcarbene, decision-maker not nearest...
Abstract We performed a comparative study on the interaction modes of 2‐haloimidazolium salts with anions in solution, particularly regard to halogen bonding, hydrogen bonding and anion–π interactions. The syntheses solid‐state analyses series sterically electronically modified structures are presented. Detailed isothermal titration calorimetry (ITC) measurements, quantum mechanics/molecular mechanics (QM/MM), classical molecular dynamics simulations (MD) free‐energy calculations together...
Abstract The polyether ionophore monensin is biosynthesized by a polyketide synthase that delivers mixture of monensins A and B the incorporation ethyl‐ or methyl‐malonyl‐CoA at its fifth module. Here we present first computational model acyltransferase domain (AT5 mon ) this synthase, thus affording an investigation basis relaxed specificity in AT5 , insights into activation for nucleophilic attack on substrate, prediction synthetic malonic acid building blocks enzyme. Our predictions are...