Homogeneous time-resolved G protein-coupled receptor-ligand binding assay based on fluorescence cross-correlation spectroscopy

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G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

The invention provides microfluidic screening systems for the identification of compounds or compositions influencing cellular transcriptomes. The invention is predicated upon taking into account differences in newly synthesized mRNA in contrast to so call ...

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

Mitochondria are essential organelles participating in numerous cellular functions, including energy harvesting, regulation of homeostasis and apoptosis. Changes in mitochondrial number, morphology, and function not only impact cellular metabolism but also ...

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we ...

Newer solid-phase peptide synthesis and release strategies enable the production of short peptides with high purity, allowing direct screening for desired bioactivity without prior chromatographic purification. However, the maximum number of peptides that ...

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

Macrocycles offer an attractive format for drug development due to their good binding properties and potential to cross cell membranes. To efficiently identify macrocyclic ligands for new targets, methods for the synthesis and screening of large combinator ...

Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

Recordings of the physiological history of cells provide insights into biological processes, yet obtaining such recordings is a challenge. To address this, we introduce a method to record transient cellular events for later analysis. We designed proteins t ...

Sample efficiency is a fundamental challenge in de novo molecular design. Ideally, molecular generative models should learn to satisfy a desired objective under minimal calls to oracles (computational property predictors). This problem becomes more apparen ...

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

Utilization of small molecules as passivation materials for perovskite solar cells (PSCs) has gained significant attention recently, with hundreds of small molecules demonstrating passivation effects. In this study, a high-accuracy machine learning model i ...

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Retinoblastoma is a rare childhood cancer of the eye. Of the small number of drugs are used to treat retinoblastoma, all have been repurposed from drugs developed for other conditions. In order to find drugs or drug combinations better suited to the improv ...

Retinoblastoma, while relatively rare, stands as the most prevalent intraocular cancer. In Switzerland, the survival rate approaches 100%, but it drops to less than 50% in low-income countries. The current treatment options for retinoblastoma rely on a lim ...

The photochemical thiol-ene reaction is an efficient method for rapid and chemoselective formation of thioether linkages under mild conditions. It has found widespread use in small-molecule synthesis as well as peptide and protein chemistry. While high-thr ...

Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...

The present invention relates to a method for analyzing cellular responsiveness to hormones or drags in a tissue sample based on an alginate-based 3D ex vivo culture system for normal and malignant tissue microstructures and uses thereof. ...

Homogeneous time-resolved G protein-coupled receptor-ligand binding assay based on fluorescence cross-correlation spectroscopy

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Antibodies expand the scope of angiotensin receptor pharmacology

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Improved microfluidic transcriptome based screening methods

Methods for high-throughput synthesis and screening of peptide libraries

Drug Screening in C. elegans to identify new pharmacological mitochondrial stress inducers

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Solid-phase peptide synthesis in 384-well plates

Computational drug development for membrane protein targets

Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation

Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization

Recording physiological history of cells with chemical labeling

Augmented Memory: Sample-Efficient Generative Molecular Design with Reinforcement Learning

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Machine Learning for Screening Small Molecules as Passivation Materials for Enhanced Perovskite Solar Cells

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers

The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma

Optimised three-dimensional in vitro retinoblastoma models tailored for drug discovery and clinical translatability

Nanomole-scale photochemical thiol-ene chemistry for high-throughput late-stage diversification of peptide macrocycles

De novo designed proteins: a study in engineering novel folds and functions

Method for hormone or drug screening in a tissue sample