Publications by authors named "Thomas M T Jensen"
Purpose: The prevalence of follow-on and compounded products of glucagon-like peptide-1 analogs is increasing. We assessed glucagon-like peptide-1 analogs semaglutide and liraglutide for purity, potential immunogenicity, and expected stability, by comparing a representative selection of commercially available follow-on drug substances (DSs) and drug products (DPs) with their corresponding originators.
Methods: Tests included several chromatography methods coupled with ultraviolet and mass spectrometry detectors, inductively coupled plasma optical emission spectroscopy, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, dissolution analyses, in silico peptide/major histocompatibility complex II-binding prediction, and fibrillation assays.
Intrinsically disordered regions in proteins often function as binding motifs in protein-protein interactions. The mechanistic aspects and molecular details of such coupled binding and folding reactions, which involve formation of multiple noncovalent bonds, have been broadly studied theoretically, but experimental data are scarce. Here, using a combination of protein semisynthesis to incorporate phosphorylated amino acids, backbone amide-to-ester modifications, side chain substitutions, and binding kinetics, we examined the interaction between the intrinsically disordered motif of amyloid precursor protein (APP) and the phosphotyrosine binding (PTB) domain of Mint2.
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- Despite advances in cancer treatments, aggressive cancers like glioblastoma (GBM) still have low survival rates, prompting research on new therapeutic targets.
- Syntenin, an intracellular scaffold protein with two PDZ domains, has been identified as a potential novel target for treating GBM.
- A new peptide inhibitor, KSL-128114, has been developed, showing strong binding to syntenin's PDZ1 domain and the ability to inhibit GBM cell viability and improve survival in animal models.
Article Synopsis
- - There is a critical need for new treatments for Alzheimer's disease (AD) that can relieve symptoms and slow progression, particularly targeting the harmful accumulation of amyloid-β (Aβ) peptides, which arise from the amyloid precursor protein (APP).
- - Previous research on Mint2, a protein that interacts with APP and the enzyme complex responsible for Aβ production, has shown mixed results on whether it promotes or inhibits Aβ generation.
- - This study clarifies that Mint2 facilitates Aβ formation and highlights a promising therapeutic strategy by using a stable peptide inhibitor to target the APP-Mint2 interaction, which could significantly lower Aβ levels in neuronal models of AD.
All proteins contain characteristic backbones formed of consecutive amide bonds, which can engage in hydrogen bonds. However, the importance of these is not easily addressed by conventional technologies that only allow for side-chain substitutions. By contrast, technologies such as nonsense suppression mutagenesis and protein ligation allow for manipulation of the protein backbone.
View Article and Find Full Text PDFThe intracellular adaptor protein Mint2 binds amyloid precursor protein (APP) and presenilin-1, which are both central constituents of the amyloidogenic pathway associated with Alzheimer's disease (AD). Additional interaction partners have also been suggested for Mint2; several of them are also pertinent to AD pathogenesis. However, no comparative mapping of the Mint2 protein-protein interaction network is available.
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