Frederik Lermyte
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View article: Native Taylor/Non‐Taylor Dispersion–Mass Spectrometry (TNT‐MS) Allows Rapid Protein Desalting and Multiplexed, Label‐Free Ligand Screening
Native Taylor/Non‐Taylor Dispersion–Mass Spectrometry (TNT‐MS) Allows Rapid Protein Desalting and Multiplexed, Label‐Free Ligand Screening Open
Native mass spectrometry (MS) is an important technique in structural biology and drug discovery, due to its ability to study non‐covalent assemblies in the gas phase. Drawbacks include the incompatibility of electrospray ionization (ESI) …
View article: Stability convergence in natural antibodies with ultra-long hypervariable loops
Stability convergence in natural antibodies with ultra-long hypervariable loops Open
Antibodies bind to antigens with hypervariable loops called complementarity-determining regions (CDRs). In contrast to conventional antibodies, a subset of bovine antibodies has an ultra-long CDR (ulCDR) composed of up to 70 residues folde…
View article: Self-packed size-exclusion columns enable versatile high-throughput native, top-down, and ion mobility-mass spectrometry studies on proteins and complexes
Self-packed size-exclusion columns enable versatile high-throughput native, top-down, and ion mobility-mass spectrometry studies on proteins and complexes Open
Native MS (nMS) is a key structural biology technique that makes it possible to study intact proteins and their interactions. Unfortunately, non-volatile salts are incompatible with nMS, which demands a laborious desalting procedure. Non-d…
View article: Discovery of fully synthetic FKBP12-mTOR molecular glues
Discovery of fully synthetic FKBP12-mTOR molecular glues Open
We discovered a fully synthetic non-degradative molecular glue for the ternary complex between FKBP12 and the FRB domain of mTOR by screening a library of FKBP12 ligands. Solving the ternary complex structure allowed significant potency en…
View article: The pivotal role of histidine 976 in human histone deacetylase 4 for enzyme function and ligand recognition
The pivotal role of histidine 976 in human histone deacetylase 4 for enzyme function and ligand recognition Open
Human histone deacetylase 4 (HDAC4) belongs to class IIa of the zinc-dependent histone deacetylases. HDAC4 is an established target for various indication areas, in particular Huntington's disease, heart failure and cancer. To reduce unwan…
View article: Discovery of fully synthetic FKBP12-mTOR molecular glues
Discovery of fully synthetic FKBP12-mTOR molecular glues Open
Molecular glues are a class of drug modalities with the potential to engage otherwise undruggable targets. However, the rational discovery of molecular glues for desired targets is a major challenge and most known molecular glues have been…
View article: MIND4OLIGOS: Determining the Monoisotopic Mass of Oligonucleotides Observed in High-Resolution Mass Spectrometry
MIND4OLIGOS: Determining the Monoisotopic Mass of Oligonucleotides Observed in High-Resolution Mass Spectrometry Open
Oligonucleotide therapeutics have emerged as an important class of drugs offering targeted therapeutic strategies that complement traditional modalities, such as monoclonal antibodies and small molecules. Their unique ability to precisely …
View article: Top-down mass spectrometry of native proteoforms and their complexes: a community study
Top-down mass spectrometry of native proteoforms and their complexes: a community study Open
View article: Design and synthesis of peptides as stabilizers of histone deacetylase 4
Design and synthesis of peptides as stabilizers of histone deacetylase 4 Open
Histone deacetylase 4 (HDAC4) contributes to gene repression by complex formation with HDAC3 and the corepressor silencing mediator for retinoid or thyroid hormone receptors (SMRT). We hypothesized that peptides derived from the class IIa …
View article: Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues
Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues Open
The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer's disease. Altered metabolism of essential biometals is another feature of Alzheimer's, with amyloid plaques representing si…
View article: Automated Flow Peptide Synthesis Enables Engineering of Proteins with Stabilized Transient Binding Pockets
Automated Flow Peptide Synthesis Enables Engineering of Proteins with Stabilized Transient Binding Pockets Open
Engineering at the amino acid level is key to enhancing the properties of existing proteins in a desired manner. So far, protein engineering has been dominated by genetic approaches, which have been extremely powerful but only allow for mi…
View article: The catalytic domain of free or ligand bound histone deacetylase 4 occurs in solution predominantly in closed conformation
The catalytic domain of free or ligand bound histone deacetylase 4 occurs in solution predominantly in closed conformation Open
Human histone deacetylase 4 (HDAC4) is a key epigenetic regulator involved in a number of important cellular processes. This makes HDAC4 a promising target for the treatment of several cancers and neurodegenerative diseases, in particular …
View article: The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues
The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues Open
Pericentric heterochromatin (PCH) forms spatio-temporarily distinct compartments and affects chromosome organization and stability. Albeit some of its components are known, an elucidation of its proteome and how it differs between tissues …
View article: The Pivotal Role of Histidine 976 in Human Histone Deacetylase 4 for Enzyme Function and Ligand Recognition
The Pivotal Role of Histidine 976 in Human Histone Deacetylase 4 for Enzyme Function and Ligand Recognition Open
View article: The need for open and FAIR data in top‐down proteomics
The need for open and FAIR data in top‐down proteomics Open
In recent years, there has been a tremendous evolution in the high‐throughput, tandem mass spectrometry‐based analysis of intact proteins, also known as top‐down proteomics (TDP). Both hardware and software have developed to the point that…
View article: Discovery of a Potent Proteolysis Targeting Chimera Enables Targeting the Scaffolding Functions of FK506‐Binding Protein 51 (FKBP51)
Discovery of a Potent Proteolysis Targeting Chimera Enables Targeting the Scaffolding Functions of FK506‐Binding Protein 51 (FKBP51) Open
The FK506‐binding protein 51 (FKBP51) is a promising target in a variety of disorders including depression, chronic pain, and obesity. Previous FKBP51‐targeting strategies were restricted to occupation of the FK506‐binding site, which does…
View article: Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogues
Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogues Open
Sulfonamides are one of the most important pharmacophores in medicinal chemistry, and sulfonamide analogues have gained substantial interest in recent years. However, the protein interactions of sulfonamides and especially of their analogu…
View article: Top-down mass spectrometry of native proteoforms and their complexes: A community study
Top-down mass spectrometry of native proteoforms and their complexes: A community study Open
The combination of native electrospray ionisation with top-down fragmentation in mass spectrometry allows simultaneous determination of the stoichiometry of noncovalent complexes and identification of their component proteoforms and co-fac…
View article: Illuminating the brain: Revealing brain biochemistry with synchrotron X-ray spectromicroscopy
Illuminating the brain: Revealing brain biochemistry with synchrotron X-ray spectromicroscopy Open
The synchrotron x-ray spectromicroscopy technique Scanning Transmission X-ray Microscopy (STXM) offers a powerful means to examine the underlying biochemistry of biological systems, owing to its combined chemical sensitivity and nanoscale …
View article: Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogs
Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogs Open
Sulfonamides are one of the most important pharmacophores in medicinal chemistry and sulfonamide analogs have gained substantial interest in recent years. However, the protein interactions of sulfonamides and especially of their analogs ar…
View article: Covalent <i>S</i>-Adenosylhomocysteine-Based DNA Methyltransferase 2 Inhibitors with a New Type of Aryl Warhead
Covalent <i>S</i>-Adenosylhomocysteine-Based DNA Methyltransferase 2 Inhibitors with a New Type of Aryl Warhead Open
The DNA methyltransferase 2 (DNMT2) is an RNA modifying enzyme associated with pathophysiological processes, such as mental and metabolic disorders or cancer. Although the development of methyltransferase inhibitors remains challenging, DN…
View article: Charge site manipulation to enhance top‐down fragmentation efficiency
Charge site manipulation to enhance top‐down fragmentation efficiency Open
In recent years, top‐down mass spectrometry has become a widely used approach to study proteoforms; however, improving sequence coverage remains an important goal. Here, two different proteins, α‐synuclein and bovine carbonic anhydrase, we…
View article: Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation
Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation Open
In order to understand protein structure to a sufficient extent for, e.g., drug discovery, no single technique can provide satisfactory information on both the lowest-energy conformation and on dynamic changes over time (the ‘four-dimensio…
View article: Biogenic metallic elements in the human brain?
Biogenic metallic elements in the human brain? Open
Discovery of nanometallic Cu 0 with Fe 0 in the human brain will fundamentally boost our understanding of neurobiology.
View article: Facile protein conjugation of platinum for light-activated cytotoxic payload release
Facile protein conjugation of platinum for light-activated cytotoxic payload release Open
This platinum anticancer complex can be conjugated to proteins, including antibodies, under mild conditions and activated by visible light, providing a basis for highly selective cancer phototherapy.
View article: Cu(<scp>iii</scp>)–bis-thiolato complex forms an unusual mono-thiolato Cu(<scp>iii</scp>)–peroxido adduct
Cu(<span>iii</span>)–bis-thiolato complex forms an unusual mono-thiolato Cu(<span>iii</span>)–peroxido adduct Open
The square-planar complex [bis(toluene-3,4-dithiolato)copper(iii)][NEt3H], characterised by X-ray photoelectron spectroscopy and DFT, fragments in FTICR-MS to form [(toluene-3,4-dithiolato)Cu(iii)(peroxide)]− by react…
View article: Roles, Characteristics, and Analysis of Intrinsically Disordered Proteins: A Minireview
Roles, Characteristics, and Analysis of Intrinsically Disordered Proteins: A Minireview Open
In recent years, there has been a growing understanding that a significant fraction of the eukaryotic proteome is intrinsically disordered, and that these conformationally dynamic proteins play a myriad of vital biological roles in both no…
View article: Multiple Protective Roles of Nanoliposome‐Incorporated Baicalein against Alpha‐Synuclein Aggregates
Multiple Protective Roles of Nanoliposome‐Incorporated Baicalein against Alpha‐Synuclein Aggregates Open
Nanoparticles are useful for increasing drug stability, solubility, and availability. The small molecule baicalein inhibits fibrillation, and detoxifies aggregates of α‐synuclein (αSN) associated with Parkinson's disease (PD), but it suffe…
View article: Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42)
Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42) Open
Atypical low-oxidation-state iron phases in Alzheimer’s disease (AD) pathology are implicated in disease pathogenesis, as they may promote elevated redox activity and convey toxicity. However, the origin of low-oxidation-state iron and the…
View article: Analysis of neuronal iron deposits in Parkinson's disease brain tissue by synchrotron x-ray spectromicroscopy
Analysis of neuronal iron deposits in Parkinson's disease brain tissue by synchrotron x-ray spectromicroscopy Open
Background
\nNeuromelanin-pigmented neurons, which are highly susceptible to neurodegeneration in the Parkinson’s disease substantia nigra, harbour elevated iron levels in the diseased state. Whilst it is widely believed that neuronal iron…