Chemically modified guide RNAs enhance CRISPR-Cas13 knockdown in human cells [0.03%]
化学修饰的导向RNA可增强II型CRISPR-Cas13在人类细胞中的敲低效果
Alejandro Méndez-Mancilla,Hans-Hermann Wessels,Mateusz Legut et al.
Alejandro Méndez-Mancilla et al.
RNA-targeting CRISPR-Cas13 proteins have recently emerged as a powerful platform to modulate gene expression outcomes. However, protein and CRISPR RNA (crRNA) delivery in human cells can be challenging with rapid crRNA degradation yielding ...
A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface [0.03%]
一种用于捕获细胞表面N连接糖蛋白结合伴侣的光交联GlcNAc类似物
Han Wu,Asif Shajahan,Jeong-Yeh Yang et al.
Han Wu et al.
N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs). Biochemical identification and characterization of glycan-mediated interactions ...
The non-canonical target PARP16 contributes to polypharmacology of the PARP inhibitor talazoparib and its synergy with WEE1 inhibitors [0.03%]
非经典靶标PARP16参与了PARP抑制剂塔拉唑帕利的多靶点特性及其与WEE1抑制剂的协同作用
Vinayak Palve,Claire E Knezevic,Daniel S Bejan et al.
Vinayak Palve et al.
PARP inhibitors (PARPis) display single-agent anticancer activity in small cell lung cancer (SCLC) and other neuroendocrine tumors independent of BRCA1/2 mutations. Here, we determine the differential efficacy of multiple clinical PARPis in...
Anthony H Keeble,Vikash K Yadav,Matteo P Ferla et al.
Anthony H Keeble et al.
There are many efficient ways to connect proteins at termini. However, connecting at a loop is difficult because of lower flexibility and variable environment. Here, we have developed DogCatcher, a protein that forms a spontaneous isopeptid...
A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype [0.03%]
一种结构特异的小分子抑制miRNA-200家族成员前体并逆转2型糖尿病表型
Hafeez S Haniff,Xiaohui Liu,Yuquan Tong et al.
Hafeez S Haniff et al.
MicroRNA families are ubiquitous in the human transcriptome, yet targeting of individual members is challenging because of sequence homology. Many secondary structures of the precursors to these miRNAs (pri- and pre-miRNAs), however, are qu...
Chemo-proteomics exploration of HDAC degradability by small molecule degraders [0.03%]
小分子降解剂介导的HDAC降解潜能的化学蛋白质组学探索
Yuan Xiong,Katherine A Donovan,Nicholas A Eleuteri et al.
Yuan Xiong et al.
Targeted protein degradation refers to the use of small molecules that recruit a ubiquitin ligase to a target protein for ubiquitination and subsequent proteasome-dependent degradation. While degraders have been developed for many targets, ...
Ligand-directed bias of G protein signaling at the dopamine D2 receptor [0.03%]
多巴胺D2受体偏向性信号转导的配体调节作用于G蛋白路径
Ee Von Moo,Kasper Harpsøe,Alexander S Hauser et al.
Ee Von Moo et al.
G-protein-coupled receptors (GPCRs) represent the largest family of drug targets. Upon activation, GPCRs signal primarily via a diverse set of heterotrimeric G proteins. Most GPCRs can couple to several different G protein subtypes. However...
Armeniaspirols inhibit the AAA+ proteases ClpXP and ClpYQ leading to cell division arrest in Gram-positive bacteria [0.03%]
亚美尼亚螺旋菌素通过抑制阳离子ClpXP和ClpYQ蛋白酶导致革兰氏阳性菌细胞分裂停滞
Puneet Labana,Mark H Dornan,Matthew Lafrenière et al.
Puneet Labana et al.
Multi-drug-resistant bacteria present an urgent threat to modern medicine, creating a desperate need for antibiotics with new modes of action. As natural products remain an unsurpassed source for clinically viable antibiotic compounds, we i...
Dymytrii Listunov,Brian M Linhares,EunGi Kim et al.
Dymytrii Listunov et al.
GAS41 is an emerging oncogene overexpressed and implicated in multiple cancers, including non-small cell lung cancer (NSCLC). GAS41 is a dimeric protein that contains the YEATS domain, which is involved in the recognition of lysine-acylated...
Structural and mechanistic investigations of protein S-glycosyltransferases [0.03%]
蛋白质S-糖基转移酶的结构和机理研究
Daisuke Fujinami,Chantal V Garcia de Gonzalo,Subhanip Biswas et al.
Daisuke Fujinami et al.
Attachment of sugars to nitrogen and oxygen in peptides is ubiquitous in biology, but glycosylation of sulfur atoms has only been recently described. Here, we characterize two S-glycosyltransferases SunS and ThuS that selectively glycosylat...