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Kinetic Analysis of Cyclization by the Substrate-Tolerant Lanthipeptide Synthetase ProcM.
ACS Catal
December 2024
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
Lanthipeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by the presence of thioether cross-links called lanthionine and methyllanthionine, formed by dehydration of Ser/Thr residues and Michael-type addition of Cys side chains onto the resulting dehydroamino acids. Class II lanthipeptide synthetases are bifunctional enzymes responsible for both steps, thus generating macrocyclic natural products. ProcM is part of a group of class II lanthipeptide synthetases that are known for their remarkable substrate tolerance, having large numbers of natural substrates with highly diverse peptide sequences.
View Article and Find Full Text PDFInsulin like growth factor 2 mRNA binding protein 2 regulates vascular development in cerebral arteriovenous malformations.
Front Neurol
December 2024
Department of Neurosurgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Background: Cerebral arteriovenous malformations (AVMs) are intricate vascular anomalies that disrupt normal cerebral blood flow, potentially leading to severe neurological complications. Although the pathology of AVMs is not fully understood, epigenetic mechanisms have been implicated in their formation.
Methods: Transcriptional differences between cerebral AVMs and normal tissues were analyzed using RNA sequencing (RNA-seq), identifying IGF2BP2 as a key differentially expressed gene.
[Current advances in the analysis of free RNA modified nucleosides by high performance liquid chromatography-tandem mass spectrometry].
Se Pu
January 2025
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;3. University of Chinese Academy of Sciences, Beijing 100049, China.
Post-transcriptional ribonucleic acid (RNA) modifications play crucial roles in regulating gene expression, with both eukaryotic and prokaryotic RNA exhibiting more than 170 distinct and ubiquitous modifications. RNA turnover generates numerous free nucleosides, including unmodified nucleosides and a variety of modified ones. Unlike unmodified nucleosides, modified nucleosides are not further degraded or used in the salvage-synthesis pathway owing to a lack of specific enzymes, which leads to the cytosolic accumulation or cellular efflux of modified nucleosides.
View Article and Find Full Text PDFDesign, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1()-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma.
J Med Chem
December 2024
Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China.
Through catalyzing the transfer of methyl groups onto the guanidinium of arginine, protein arginine methyltransferase 5 (PRMT5) was essential to the cell growth of cancer cells. By utilizing a scaffold hopping strategy, a novel series of 3,4-dihydroisoquinolin-1()-one derivatives were designed and synthesized. Through a systematic SAR study, demonstrated excellent PRMT5 inhibitory activity, potent antiproliferative activity against Z-138, favorable pharmacokinetic profiles, and low hERG toxicity.
View Article and Find Full Text PDFA practical, biomimetic, one-pot synthesis of firefly luciferin.
Sci Rep
December 2024
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
The bioluminescence reaction of firefly luciferase with D-luciferin has become an indispensable imaging technique in modern biology and life science experiments, but the high cost of D-luciferin is limiting its further application. Here, we report a practical, one-pot synthesis of D-luciferin from p-benzoquinone (p-BQ), L-cysteine methyl ester and D-cysteine, with an overall yield of 46%. Our route, which is six steps in length and proceeds via 2-cyano-6-hydroxybenzothiazole, is inspired by the mechanistic study of our previously reported biomimetic, non-enzymatic, one-pot formation of L-luciferin from p-BQ and L-cysteine.
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