ChemRxiv Released a Study of Diverse Heteroarene Stacking Under Physiological Conditions with Several of Viva Biotech's R&D Teams' Participation
Time: 2023-01-11
Source: Viva Biotech
[Abstract]:The publication of these findings reflects Viva's professional R&D capabilities and comprehensive service capabilities.

Recently, Dr. Steven E. Wheeler of the University of Georgia and Dr. Adam R. Renslo of the University of California, San Francisco jointly published a paper on ChemRxiv titled "A Comprehensive Empirical-Computational Study of Diverse Heteroarene Stacking under Physiological Conditions." The study examines a series of ligand molecules containing heteroaromatics and their ability to bind procaspase-6 dimer. The binding mode is confirmed through crystal structure analysis, and the equilibrium dissociation constant (Kd) of the interaction is determined using surface plasmon resonance (SPR) technology. From this, the experimental binding free energy is calculated, and the binding affinity is predicted computationally, allowing for the examination of heteroarene stacking interactions under physiological conditions. This research is the result of a successful collaboration between biomedical start-ups, universities, and CRO companies. As a world's leading one-stop CRO/CDMO, Viva Biotech has been working closely with Elgia Therapeutics, a Viva portfolio company, since 2020 in providing chemical synthesis, protein preparation, structural analysis, SPR services, and more to support this joint collaboration for the research. The publication of these findings reflects Viva's professional R&D capabilities and comprehensive service capabilities.


( Source: ChemRxiv )


The abstract of the paper states: “Heteroaromatic stacking interactions help stabilize protein tertiary structure and are important in drug binding, supramolecular chemistry, and materials science. Although diverse computational and experimental approaches have been utilized to study these interactions, a broadly useful protein–ligand model system has yet to emerge, despite laudable efforts by Diederich and co-workers in this vein. Here the studies of  thirty synthetic ligands present diverse heteroarene probes for stacking between symmetry-related tyrosine residues at the dimer interface of procaspase-6. Authors demonstrate crystallographically that stacking geometries are highly conserved across the ligand test set and show with high-accuracy computations that differences in ligand binding free energies are primarily attributable to the relative strength of the stacking interactions. The empirical results are discussed in light of recent computational studies of these interactions, including the effects of torsional strain, heteroarene tautomeric state, and co-axial orientation of stacking groups. Overall, this study provides an extensive dataset of empirical and high-level computed binding energies in a versatile new protein–ligand system highly amenable to studies of other intermolecular interactions.”1


Dr. Deqian Sun, Associate Director of the Department of Chemistry at Viva Biotech, stated that "finding a more universally effective protein-ligand model system for heteroarene stacking interactions has long been a challenging problem for scientists. The Viva chemistry team is pleased to be part of the team in the synthesis of procaspase-6 dimer ligand molecules for this study. Viva's chemical synthesis platform has provided efficient and reliable synthesis services to our customers, successfully completed the synthesis of all ligand compounds required for research.”


Dr. Yanlong Zhao, Senior Director of the Biological Department at Viva Biotech, stated: "We have closely collaborated with Elgia Therapeutics on protein production and structural research, and this has been a very valuable experience for the Viva Biotech team. Leveraging our strong protein research capabilities, we efficiently expressed and purified procaspase-6 trimer through a comprehensive protein expression system, ensuring the stability and uniformity of the protein sample at the source, and providing a solid foundation for the structural analysis of the target protein.”


According to Mr. Jingjing Yang, Associate Director of the Biological Department at Viva Biotech, "Our SPR team provides efficient compound and protein affinity testing from early experiment design to subsequent data delivery. For this new target, there were no previous SPR experiments as references, so we innovatively designed a detection method specifically for the target. Based on unique automated sample preparation of Viva’s SPR and the Biacore 8K high-throughput screening platform, the efficiency of compound screening has been greatly improved."


1. Canan S, Togo T, Tram L, Denton L, ElHilali-Pollard X, Gu J, et al. A Comprehensive Empirical–Computational Study of Diverse Het-eroarene Stacking under Physiological Conditions. ChemRxiv. Cambridge: Cambridge Open Engage; 2022; This content is a preprint and has not been peer-reviewed.


About Elgia Therapeutics


Elgia Therapeutics is a venture-backed biopharmaceutical company pioneering novel molecular approaches for the treatment of metabolic, inflammatory, and fibrotic diseases. The members of the Elgia leadership team are world-renowned scientists with synergistic expertise in innate immunity, metabolic syndromes, inflammatory processes, and drug discovery.

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