Protein N-terminal methyltransferases (NTMTs) methylate the α-N-terminal amines of proteins starting with the canonical X-P-K/R motif. Genetic studies imply that NTMT1 regulates cell mitosis and DNA damage repair. Herein, we report the rational design and development of the first potent peptidomimetic inhibitor for NTMT1/2. Biochemical and cocrystallization studies manifest that (with a half-maximal inhibitory concentration of 0.89 ± 0.10 μM) is a competitive inhibitor to the peptide substrate and noncompetitive to the cofactor S-adenosylmethionine. exhibits over 100-fold selectivity to NTMT1/2 among a panel of 41 MTs, indicating its potential to achieve high selectivity when targeting the peptide substrate binding site of NTMT1/2. Its cell-permeable analogue (IC of 54 ± 4 nM) decreases the N-terminal methylation level of the regulator of chromosome condensation 1 and SET proteins in HCT116 cells. This proof-of principle study provides valuable probes for NTMT1/2 and highlights the opportunity to develop more cell-potent inhibitors to elucidate the function of NTMTs in the future.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486280 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.0c00689 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An ultrasensitive colorimetric/fluorescent/photothermal sensing platform for the detection of D-amino acids based on carbon dots nanozymes with enhanced peroxidase-like activity.
Mikrochim Acta
January 2025
Department of Chemistry, School of Science, Xihua University, Chengdu, 610039, PR China.
Based on the enhanced peroxidase-like activity of carbon dots nanozymes (CDszymes), with a specific oxidation reaction of D-amino acid oxidase catalysing the formation of HO from D-amino acid, an ultrasensitive sensing platform, was constructed for the quantitative detection of D-amino acids in saliva. With the increase of D-amino acids concentration, the blue color of catalytic product gradually deepend, the fluorescence CDszymes gradually quenched, and the temperature gradually increased. Using D-alanine as D-amino acid models, the detection limits of D-alanine in colorimetric/photothermal/fluorescent mode were 0.
View Article and Find Full Text PDFSingle atom alloys aggregation in the presence of ligands.
Nanoscale
January 2025
Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Single atom alloys (SAAs) have gained tremendous attention as promising materials with unique physicochemical properties, particularly in catalysis. The stability of SAAs relies on the formation of a single active dopant on the surface of a metal host, quantified by the surface segregation and aggregation energy. Previous studies have investigated the surface segregation of non-ligated and ligated SAAs to reveal the driving forces underlying such phenomena.
View Article and Find Full Text PDFTuning the local S coordination environment on Ru single atoms to boost the oxygen evolution reaction.
Nanoscale
January 2025
School of Chemistry, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
Engineering the local electronic structure of single atom catalysts (SACs) still remains challenging. In this study, a Ru-NiS single atom catalyst with a controlled S coordination environment, where Ru single atoms are implanted on a NiS nanoflower consisting of plenty of cross-linked nanosheets, has been developed a facile atom capture strategy. Using Density Functional Theory (DFT) calculations, it has been revealed that the fine-tuned local S coordination environment can optimize the electronic structure of Ru active sites, and reduce the energy barrier of the rate-determining step for the oxygen evolution reaction (OER), thus boosting the electrocatalytic activity, such as a low overpotential of 269 mV at 10 mA cm.
View Article and Find Full Text PDFLowering Linker Symmetry to Access Zirconium Metal-Organic Frameworks for Inverse Alkane/Alkene Separations.
Angew Chem Int Ed Engl
January 2025
Northwestern University, Department of Chemistry, UNITED STATES OF AMERICA.
Enriching the structural diversity of metal-organic frameworks (MOFs) is of great importance in developing functional porous materials with specific properties. New MOF structures can be accessed through the rational design of organic linkers with diverse geometric conformations, and their structural complexity can be enhanced by choosing linkers with reduced symmetry. Herein, a series of Zr-based MOFs with unprecedented topologies were developed through a linker desymmetrization and conformation engineering approach.
View Article and Find Full Text PDFPhotoinduced Difluoromethylation Cyclization to Generate Medium-Sized Difluoro-benzo[]azepines.
Org Lett
January 2025
School of Pharmacy, Yantai University, Yantai 264005, P. R. China.
Compared with the energetically favorable 5- or 6-membered fluoro-functionalized heterocycles, the construction of medium-sized fluoro-heterocycles is relatively under-researched because of their inherently unfavorable enthalpic and entropic nature. Based on rational design and DFT calculations, a novel photocatalytic difluoromethyl radical-initiated intramolecular 7--trig cyclization was realized, thus affording a sustainable route for the synthesis of challenging fluoro-functionalized medium-sized -heterocycles. Depending on atomic dipole moment corrected Hirshfeld population (ADCH) charge calculations, the chemoselective 6--trig radical cyclizations were further replenished.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!