Results 131 to 140 of about 3,750,504 (279)

Hederagenin Attenuates Morphine Addiction via GABAA1‐Mediated Modulation of Ca2+–CaMK–CREB Signaling in Ventral Tegmental Dopaminergic Neurons

Advanced Science, EarlyView.
Hederagenin is identified as a GABAA1‐targeting natural compound that suppresses morphine‐associated reward by restraining Ca2+–CaMK–cAMP–CREB signaling in ventral tegmental dopaminergic neurons. RVG29‐modified liposomal delivery further enhances brain accumulation and behavioral efficacy, providing a mechanistically defined strategy for natural ...
Hongyang Jiang, Ziting Zhou, Nannan Xue, Jiasi Deng, Yuanyuan Zhou, Xinying Lv, Yuxuan Wang, Yi Zhang, Haotian Pan, Geyan Xu, Yinkun Tao, Mengran Li, Xin Cui, Hongyue Ma, Qian Wang, Zhigang Lu   +15 more
wiley   +1 more source

Beyond Nature's Blueprint: Macrocyclic Peptides Containing Unnatural Amino Acids in Therapeutic Development

Angewandte Chemie, EarlyView.
Strategic incorporation of unnatural amino acids transforms macrocyclic peptides into drug‐like molecules capable of engaging challenging targets. These building blocks enhance stability, permeability, and bioavailability, accelerating the development of next‐generation peptide therapeutics.
Krishna K. Sharma, Komal Sharma, Anku Sharma, Kamya Rao, Rahul Jain, Brett VanVeller   +5 more
wiley   +2 more sources

Identification of a β-arrestin-biased negative allosteric modulator for the β₂-adrenergic receptor. [PDF]

Proc Natl Acad Sci U S A, 2023
Ippolito M, De Pascali F, Hopfinger N, Komolov KE, Laurinavichyute D, Reddy PAN, Sakkal LA, Rajkowski KZ, Nayak AP, Lee J, Lee J, Cao G, Donover PS, Reichman M, An SS, Salvino JM, Penn RB, Armen RS, Scott CP, Benovic JL.   +19 more
europepmc   +1 more source

A Robust Process for an mGluR5 Negative Allosteric Modulator: Difluoromethylation and Sonogashira Coupling on Large Scale

, 2016
The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a ...
Mahmut Levent (2023186), Mousumi Ghosh (306838), Steven M. Hoagland (2023183), Richard J. Varsolona (1458094), Roger M. Farr (2023180), Jeffrey B. Sperry (1702318), Karen Sutherland (1458145)   +6 more
core   +1 more source

Co‐activation of Selective Nicotinic Acetylcholine Receptor Subtypes Is Required for Neuroprotection against Alzheimer's Disease

Advanced Science, EarlyView.
ABSTRACT Beta‐amyloid peptide (Aβ)‐induced suppression of hippocampal GABAergic interneuron activity drives hyperexcitability, amyloid pathology, and cognitive impairment in Alzheimer's disease (AD), suggesting that enhancing hippocampal inhibition may be protective.
Rahmi Lee, Gayeon Kim, Ellison R. Black, Seonil Kim   +3 more
wiley   +1 more source

Distinct Molten‐Globule Conformations in an Interacting Protein Domain Resolved by 19F NMR of Fluoroproline Residues

Angewandte Chemie, EarlyView.
Modifying the conformational ensemble of “molten‐globule” protein by the site‐specific incorporation of stereoisomeric 4‐fluoroproline residues modulated its binding affinity and aggregation behavior. 19F NMR spectroscopy enabled the detection of key interactions responsible for structural and dynamic changes. ABSTRACT Recently, the application of deep
Abir Ben Bouzayene, Mariam Sai, Alexis Jouin, Yves Nominé, Vladimir Torbeev, Bruno Kieffer   +5 more
wiley   +2 more sources

Discovery of MK-8768, a Potent and Selective mGluR2 Negative Allosteric Modulator. [PDF]

ACS Med Chem Lett, 2023
Rudd MT, Manley PJ, Hanney B, Meng Z, Shu Y, de Leon P, Frie JL, Han Y, Wai JM, Yang ZQ, Perkins JJ, Hurzy DM, Manikowski JJ, Zhu H, Bungard CJ, Converso A, Meissner RS, Cosden ML, Hayashi I, Ma L, O'Brien J, Uebele VN, Schachter JB, Bhandari N, Ward GJ, Fillgrove KL, Lu B, Liang Y, Dubost DC, Puri V, Eddins DM, Vardigan JD, Drolet RE, Kern JT, Uslaner JM.   +34 more
europepmc   +1 more source

FBP1‐Mediated Compartmentalization of Glycolytic Enzyme Complexes Suppresses PKM2 Function to Ameliorate MASLD Progression

Advanced Science, EarlyView.
In normal hepatocytes, FBP1 forms compartmentalized complexes with PKM2, ENO1, and LDHA independent of its catalytic activity, inhibiting PKM2 activity and restricting excessive glycolysis. During MASLD progression, FBP1 downregulation markedly reduces the abundance of these complexes and releases the “hijacked” glycolytic enzymes, leading to PKM2 ...
Busong Wang, Yiping Tang, Na Li, Xuening Dai, Jing Wu, Bin Xue, Yuxin Chen, Jingzi Zhang, Lingdong Kong, Chaojun Li, Lei Fang   +10 more
wiley   +1 more source

Transport–Reaction–Signal Coupling in Lateral Flow Assays for Next‐Generation Point‐of‐Care Diagnostics

Advanced Science, EarlyView.
Lateral flow assays are evolving into interdisciplinary, system‐level sensing platforms. Recent innovations are deconstructed through coupled phases of mass transfer, reaction, and signal transduction, revealing interdependence across porous materials, interfacial chemistry, nanolabels, readout devices, and data‐enabled analysis.
Yan Pan, Yuewei Li, Chao Mi, Zhengwen Yang, Lana McClements, Steven J. Langford, Jiayan Liao   +6 more
wiley   +1 more source

Machine learning approaches in predicting allosteric sites [PDF]

Allosteric regulation is a fundamental biological mechanism that can control critical cellular processes via allosteric modulator binding to protein distal functional sites.
Zoe, Cournia, Francho, Nerín-Fonz
core   +2 more sources