Results 141 to 150 of about 121,181 (303)

Nucleic Acid Therapeutics for “Undruggable” Cancer Targets: Mechanisms, Challenges, and Prospects

Advanced Science, EarlyView.
Nucleic acid therapeutics bypass the structural limitations of conventional drugs by targeting mRNA rather than proteins. This review examines how antisense oligonucleotides, siRNAs, miRNAs, aptamers, and mRNA vaccines intervene against historically undruggable oncoproteins including Ras, MYC, and p53, highlighting mechanistic advances, delivery ...
Feng Xu, Ke Wang, Kaizhong Lu, Tianlun Hou, Yuan Chen, Xian Wang, Hongchuan Jin   +6 more
wiley   +1 more source

AND‐Logic‐Gated Aptamer Switch for Precise Targeting and Regulation of RNA G‐Quadruplexes

Angewandte Chemie, EarlyView.
An AND‐logic‐gated aptamer switch enables tumor‐selective activation of RNA G‐quadruplex (rG4)‐targeting function. By combining cell‐surface recognition and intracellular redox sensing, the system achieves precise regulation of disease‐relevant RNA structures exclusively in tumor cells, with minimal off‐target effects in normal cells, offering a ...
Dan Wang, Ying Feng, Chun Kit Kwok
wiley   +2 more sources

Small-angle neutron scattering studies on the AMPA receptor GluA2 in the resting, AMPA-bound and GYKI-53655-bound states

IUCrJ, 2018
The AMPA receptor GluA2 belongs to the family of ionotropic glutamate receptors, which are responsible for most of the fast excitatory neuronal signalling in the central nervous system. These receptors are important for memory and learning, but have also
Andreas Haahr Larsen, Jerzy Dorosz, Thor Seneca Thorsen, Nicolai Tidemand Johansen, Tamim Darwish, Søren Roi Midtgaard, Lise Arleth, Jette Sandholm Kastrup   +7 more
doaj   +1 more source

Synthesis and preliminary studies of a novel negative allosteric modulator [11C]QCA for imaging of metabotropic glutamate receptor 2

ACS Chemical Neuroscience, 2017
Metabotropic glutamate 2 receptors (mGlu2) are involved in the pathogenesis of several CNS disorders and neurodegenerative diseases. Pharmacological modulation of this target represents a potential disease-modifying approach for the treatment of ...
Xiaofei Zhang, K. Kumata, Tomoteru Yamasaki, Ran Cheng, A. Hatori, Longle Ma, Yiding Zhang, Lin Xie, Lu Wang, H. Kang, Douglas J. Sheffler, N. Cosford, Ming-Rong Zhang, Steven H. Liang   +13 more
semanticscholar   +1 more source

Transformation of Pro-Leu-Gly-NH₂ Peptidomimetic Positive Allosteric Modulators of the Dopamine D₂ Receptor into Negative Modulators

, 2016
The synthesis of dimethyl derivatives of 5.6.5 spiro bicyclic lactam Pro-Leu-Gly-NH2 peptidomimetics was carried out to test the hypothesis that by placing methyl groups on the β-methylene carbon of the thiazolidine ring steric bulk would be introduced ...
Rodney L. Johnson (442506), Ram K. Mishra (442507), Swapna Bhagwanth (2091793), Satyendra Mishra (308953), Ritesh Daya (2091799), Jordan Mah (2091796)   +5 more
core   +1 more source

Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies

Advanced Science, EarlyView.
In this review, an integrated conceptual framework linking HSP90's molecular chaperone functions to its pathological roles in cancer is proposed. HSP90 serves as a central node that integrates oncogenic signaling, buffers proteotoxic stress, maintains cancer stem cell plasticity, and shapes tumor‐immune interactions, all of which converge to drive ...
Beibei Zhang, Xinxin Zou, Jiansong Zhou, Qinmiao Sun, Dahua Chen   +4 more
wiley   +1 more source

DNA‐Induced Entropic Gain Triggers an Allosteric Switch for Biomolecular Condensation of Heat Shock Transcription Factor 1

Angewandte Chemie, EarlyView.
Hsf1 undergoes phase separation around target DNA, activating stress‐responsive transcription. DNA binding tunes conformational dynamics of Hsf1DBD, which propagates through large‐scale domain rearrangements involving DBD–IDR interactions to regulate phase separation. This hierarchical framework illustrates how local structural events at the side chain
Soichiro Kawagoe, Hiroyuki Kumeta, Tomohide Saio   +2 more
wiley   +2 more sources

ProSiteHunter: A Unified Framework for Sequence‐Based Prediction of Protein‐Nucleic Acid and Protein‐Protein Binding Sites

Advanced Science, EarlyView.
This study proposed a unified sequence‐based framework for protein binding site prediction, which adopted a tri‐track semantic multi‐source feature fusion strategy to effectively capture diverse macromolecular interaction sites and further improved the accuracy of antibody‐antigen interaction prediction.
Dongliang Hou, Qihang Zhen, Zexin Lv, Xinyue Cui, Suhui Wang, Minghua Hou, Zhan Zhou, Xiaogen Zhou, Guijun Zhang   +8 more
wiley   +1 more source

Effect of cooperativity factor γ on the interaction of two allosteric modulators binding each to its own allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence two allosteric modulators A and B each binding to its own site, where A is either positive (left) or negative (right) and B is negative allosteric modulator.
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

A Brain‐Penetrant Nanobody Reveals GSK3β‐Driven Proline‐Directed Phosphorylation as a Master Regulator of Ischemic Neurodegeneration

Advanced Science, EarlyView.
A brain‐targeted nanoparticle enables delivery of a therapeutic nanobody (Nb.29E9) that inhibits pathogenic GSK3β signaling. This intervention restores AMPK/mTORC1/TGFβ homeostasis, attenuates neuroinflammation and oxidative stress, and promotes long‐term functional recovery after ischemic stroke.
Lan Li, Muyang Li, Lei Sun, Ying Yang, Yuanshun Wu, Ziyi Yin, Anni Wang, Peiyang Zhou, Shaoxiang Luo, Jian Chen, Jun Qin, Zhibing Ai, Zilong Yuan, Zhiqiang Dong, Min Zhang   +14 more
wiley   +1 more source