Publications related to Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries

Related publications (30)

Methods for high-throughput synthesis and screening of peptide libraries

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 ...

EPFL2024

Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation

Christian Heinis, Alessandro Angelini, Alexander Lund Nielsen, Mischa Schüttel, Manuel Leonardo Merz, Xinjian Ji, Anne Sofie Luise Zarda, Ganesh Kumar Mothukuri, Zsolt Bognár, Edward Jeffrey Will

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 ...

Wiley-VCH Verlag GmbH2024

Deconvolution of ex-vivo drug screening data and bulk tissue expression predicts the abundance and viability of cancer cell subpopulations

Alexandre Coudray

Ex-vivo drug sensitivity screening (DSS) allows the prediction of cancer treatment effectiveness in a personalized fashion. However, it only provides a readout on mixtures of cells, potentially occulting important information on clinically relevant cell su ...

EPFL2023

Oxidation processes and me

Urs von Gunten

This publication summarizes my journey in the field of chemical oxidation processes for water treatment over the last 30+ years. Initially, the efficiency of the application of chemical oxidants for micropollutant abatement was assessed by the abatement of ...

Pergamon-Elsevier Science Ltd2024

Palladium-based supramolecular assemblies: from complex structures to water-soluble anion-receptors

Sylvain Alexandre Marie Sudan

The combination of palladium salts and bipyridyl ligands can lead to the formation of a large variety of coordination complexes, with different shapes and sizes, displaying a very versatile host-guest chemistry. Increasing their structural complexity remai ...

EPFL2024

Augmenting large language models with chemistry tools

Andres Camilo Marulanda Bran, Carlo Baldassari, Philippe Schwaller, Oliver Tobias Schilter

Large language models (LLMs) have shown strong performance in tasks across domains but struggle with chemistry-related problems. These models also lack access to external knowledge sources, limiting their usefulness in scientific applications. We introduce ...

Nature Portfolio2024

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

Philippe Schwaller, Jeff Guo

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 ...

Amer Chemical Soc2024

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

Irina Sinenko

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 ...

EPFL2023

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

Christoph Bostedt, Camila Bacellar Cases Da Silveira

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 ...

Nature Portfolio2023

Artificial intelligence for natural product drug discovery

Philippe Schwaller, Albert Hofstetter, Michael Alexander Skinnider, Florian Huber

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to e ...

Nature Portfolio2023

Development of methods for the synthesis of large combinatorial libraries of macrocyclic compounds

Mischa Schüttel

Macrocycles have raised much interest in the pharmaceutical industry due to their ability to bind challenging targets while often still being able to cross membranes to reach intracellular proteins. However, the development of macrocyclic ligands to new di ...

EPFL2023

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

Alexander Lund Nielsen, Mischa Schüttel

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 ...

WILEY2023

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

Paul Joseph Dyson, Irina Sinenko, Roland Christopher Turnell-Ritson

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 ...

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD2023

Method for hormone or drug screening in a tissue sample

Cathrin Brisken, Christoph Merten, Yueyun Zhang

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. ...

2023

Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale

Christian Heinis, Gerardo Turcatti, Alessandro Angelini, Jonathan Patrice Vesin, Julien Bortoli Chapalay, Manuel Leonardo Merz, Sevan Mleh Habeshian, Mischa Schüttel, Ganesh Kumar Mothukuri, Gontran Sangouard, Cristina Diaz Perlas, Zsolt Bognár

Macrocycles have excellent potential as therapeutics due to their ability to bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, ...

Nature Research2022

Generating macrocyclic inhibitors of protein-protein interactions

Gontran Sangouard

Protein-protein interactions (PPIs) play important roles in many diseases and their modulation is an attractive strategy for developing new therapeutics. However, the relatively large and often flat binding surfaces of PPIs makes the development of inhibit ...

EPFL2022

A microfluidic Braille valve platform for on-demand production, combinatorial screening and sorting of chemically distinct droplets

Vida Vafaizadeh, Christoph Merten

Droplet microfluidics is a powerful tool for a variety of biological applications including single-cell genetics, antibody discovery and directed evolution. All these applications make use of genetic libraries, illustrating the difficulty of generating che ...

NATURE PORTFOLIO2022

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, i ...

EPFL2022

Identification of a Heteroleptic Pd6L6L′6 Coordination Cage by Screening of a Virtual Combinatorial Library

Rosario Scopelliti, Kay Severin, Farzaneh Fadaei Tirani, Suzanne Maria Jansze, Rujin Li, Sylvain Alexandre Marie Sudan

The design of structurally defined heteroleptic coordination cages is a challenging task, and only few examples are known to date. Here we describe a selection approach that allowed the identification of a novel hexanuclear Pd cage containing two types of ...

2021

High-content, targeted RNA-seq screening in organoids for drug discovery in colorectal cancer

Jörg Hülsken, Maxim Norkin

Organoids allow the recapitulation of intestinal homeostasis and cancerogenesis in vitro; however, RNA sequencing (RNA-seq)-based methods for drug screens are missing. We develop targeted organoid sequencing (TORNADO-seq), a high-throughput, high-content d ...

2021