Search

Proximity Biosensor Assay for PROTAC Ternary Complex Analysis

Irene Ponzo, Alice Solda, Charlotte Crowe, Goran Dahl, Stefan Geschwindner, Alessio Ciulli, Ulrich Rant

Version 1 posted 06 March 2024

Ternary complexes , consisting of two proteins connected by small molecules like PROTACs or molecular glues pose new challenges for the analysis of molecular interactions, because they depend not only on binary affinities, but are orchestrated by cooperativity and avidity effects. Here, we introduce a proximity binding assay for the simultaneous measurement of binary and ternary interaction kinetics on a biosensor surface. Target proteins and ubiquitin E3 ligase substrate receptors are tethered to mobile swivel arms of a Y-shaped DNA scaffold, which presents them in close proximity to PROTAC

1,640

Downloads

Polymer Science

Working Paper

Monomer-Recyclable Polyesters From CO2 and 1,3-Butadiene

Jialin Xu, Yuxuan Niu, Bo-Lin Lin

Version 2 posted 13 March 2024

NOTE：This paper was first submitted for peer review at 31-Jan-2024 , Manu-script ID: ja-2024 -01537k. Recently, we found a very similar work published on ChemRxiv DOI : 10.26434 /chemrxiv -2024 -0p22l, therefore we decide to publish our work on ChemRxiv

358

Downloads

Biological and Medicinal Chemistry

Working Paper

Ternary Complex-Templated Dynamic Combinatorial Chemistry for the Selection and Identification of Homo-PROTACs

Claudia Diehl, Alessandra Salerno, Alessio Ciulli

Version 2 posted 09 April 2024

Ternary complex templated dynamic combinatorial libraries allowed identification of novel Homo-PROTAC degraders. We anticipate future applications of ternary -complex directed DCC to early PROTAC screenings and expansion to other proximity -inducing modalities beyond PROTACs

1,268

Downloads

Biological and Medicinal Chemistry

Working Paper

Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay

Guilherme Castro, Alessio Ciulli

Version 1 posted 21 June 2021

Cooperativity is an important parameter to understand the ternary complexes formed by protein degraders. We developed fluorine NMR competition binding experiments to determine cooperativity of PROTACs . We show applicability to estimate both positive and negative cooperativity, also with homo-dimerizers, and highlight key features and considerations for optimal assay

696

Downloads

Biological and Medicinal Chemistry

Working Paper

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

Satomi Imaide, Kristin M. Riching, Nikolai Makukhin, Vesna Vetma, Claire Whitworth, Scott J. Hughes, Nicole Trainor, Sarah D. Mahan, Nancy Murphy, Angus Cowan, Kwok-Ho Chan, Conner Craigon, Andrea Testa, Chiara Maniaci, Marjeta Urh, Danette L. Daniels, Alessio Ciulli

Version 2 posted 20 October 2021

Bivalent PROTACs work drive protein degradation by simultaneously binding a target protein and an E3 ligase and forming a productive ternary complex . We hypothesized that increasing binding valency within a PROTAC could enhanced degradation. Here, we designed trivalent PROTACs consisting of a bivalent BET inhibitor and an E3 ligand, tethered via a branched linker. We identified VHL-based SIM1 as a low picomolar BET degrader, with preference for BRD2. Compared to bivalent PROTACs

4,490

Downloads

Organic Chemistry

Working Paper

Reply to the Comment on “On the SN2 Reactions Modified in Vibrational Strong Coupling Experiments: Reaction Mechanisms and Vibrational Mode Assignments”

Clàudia Climent, Johannes Feist

Version 1 posted 28 April 2021

Ebbesen, 2020, DOI :10.26434 /chemrxiv .12982358.v1.) on our recent paper (C . Climent and J. Feist, Phys. Chem. Chem. Phys., 2020, 22, 23545) had been posted to ChemRxiv

471

Downloads

2

Citations

Biological and Medicinal Chemistry

Working Paper

Site-selective enzymatic C‒H amidation for synthesis of diverse lactams

Inha Cho, Zhijun Jia, Frances H. Arnold

Version 2 posted 03 January 2020

The original paper can be accessed by selecting “Version 1” of the preprint below, or by accessing https://doi.org/10.26434 /chemrxiv .7711418.v1. Inha Cho, Zhi-Jun Jia, Frances H. Arnold*Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.*Corresponding author. Email: [email protected]. I

2,688

Downloads

Theoretical and Computational Chemistry

Working Paper

In Silico Modeling and Scoring of PROTAC-Mediated Ternary Complex Poses

Junzhuo Liao, Xueqing Nie, Ilona Unarta, Spencer Ericksen, Weiping Tang

Version 3 posted 20 December 2021

Proteolysis targeting chimeras (PROTACs ) are bifunctional molecules that induce ubiquitination and subsequent degradation of proteins via formation of ternary complexes between an E3 ubiquitin ligase and a target protein. Rational design of PROTACs requires accurate knowledge of the native configuration of the PROTAC induced ternary complex . This study demonstrates that native and non-native ternary complex

1,962

Downloads

Theoretical and Computational Chemistry

Working Paper

Non-Markovian Dynamic Models Identify Non-Canonical KRAS-VHL Encounter Complex Conformations for Novel PROTAC Design

Yunrui Qiu, Rafal P. Wiewiora, Jesus A. Izaguirre, Huafeng Xu, Woody Sherman, Weiping Tang, Xuhui Huang

Version 1 posted 11 June 2024

One notable method for TPD is Proteolysis Targeting Chimeras (PROTACs , or heterobifunctional degraders) that selectively degrade a protein of interest (POI) through E3-ligase induced ubiquitination followed by proteasomal degradation. PROTACs utilize a warhead-linker-ligand architecture to bring the POI (bound to the warhead) and the E3 ligase (bound to the ligand) into close proximity . The resulting non-native protein-protein interactions (PPIs) formed between the POI and E3 ligase lead to the formation of a stable POI-degrader-ligase ternary complex

542

Downloads

Theoretical and Computational Chemistry

Working Paper

Construction of PROTAC-Mediated Ternary Complex Structure Distribution Profiles Using Extensive Conformational Search

Genki Kudo, Takumi Hirao, Ryuhei Harada, Yasuteru Shigeta, Takatsugu Hirokawa, Ryunosuke Yoshino

Version 1 posted 17 April 2024

Proteolysis-targeting chimeras (PROTACs ) are heterobifunctional small molecules that recruit E3 ubiquitin ligases to a target protein and induce its ubiquitination by forming a ternary complex . For rational PROTAC design, computational methods that provide molecular insights into these association structures are required. In this study, we attempted extensive conformational search of PROTAC -mediated ternary complex

293

Downloads

Refine Search

25392 results for search term: Ponzo I., Solda A., Crowe C., Dahl G., Geschwindner S.*, Ciulli A.*, Rant U.* Proximity Biosensor Assay for PROTAC Ternary Complex Analysis. ChemRxiv. 2024; doi: 10.26434/chemrxiv-2024-8w4zb

Proximity Biosensor Assay for PROTAC Ternary Complex Analysis

Extract found to contain search terms

Monomer-Recyclable Polyesters From CO2 and 1,3-Butadiene

Extract found to contain search terms

Ternary Complex-Templated Dynamic Combinatorial Chemistry for the Selection and Identification of Homo-PROTACs

Extract found to contain search terms

Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay

Extract found to contain search terms

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

Extract found to contain search terms

Reply to the Comment on “On the SN2 Reactions Modified in Vibrational Strong Coupling Experiments: Reaction Mechanisms and Vibrational Mode Assignments”

Extract found to contain search terms

Site-selective enzymatic C‒H amidation for synthesis of diverse lactams

Extract found to contain search terms

In Silico Modeling and Scoring of PROTAC-Mediated Ternary Complex Poses

Extract found to contain search terms

Non-Markovian Dynamic Models Identify Non-Canonical KRAS-VHL Encounter Complex Conformations for Novel PROTAC Design

Extract found to contain search terms

Construction of PROTAC-Mediated Ternary Complex Structure Distribution Profiles Using Extensive Conformational Search

Extract found to contain search terms

25392 results for search term: **Ponzo I., Solda A., Crowe C., Dahl G., Geschwindner S., Ciulli A., Rant U.* Proximity Biosensor Assay for PROTAC Ternary Complex Analysis. ChemRxiv. 2024; doi: 10.26434/chemrxiv-2024-8w4zb**