MicroED as a powerful tool for structure determination of macrocyclic drug compounds directly from their powder formulations.

E Danelius, G Bu, H Wieske, T Gonen

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Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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0 citing papers in PubMed.

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4 · The record

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MicroED as a Powerful Tool for Structure Determination of Macrocyclic Drug Compounds Directly from Their Powder Formulations.2023

5 · Who and what money

Authors and funding

4 authors.

E DaneliusHoward Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.

G BuDepartment of Biological Chemistry, University of California Los Angeles, 615 Charles E.Young Drive South, Los Angeles, CA 90095, USA.

H WieskeDepartment of Chemistry - BMC, Uppsala University, Husargatan 3, 75237 Uppsala, Sweden.

T GonenHoward Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.

Funding

TRD4: Design and Engineering of MicroED hardware for nanocrystallization and time resolved studiesP41GM136508 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GONEN, TAMIR, NANNENGA, BRENT · 2020 to 2024

$7.6M

NIGMS NIH HHS P41 GM136508

6 · The paper itself

Abstract

Macrocycles are important drug leads with many advantages including the ability to target flat and featureless binding sites as well as act as molecular chameleons and thereby reach intracellular targets. However, due to their complex structures and inherent flexibility, macrocycles are difficult to study structurally and there are limited structural data available. Herein, we use the cryo-EM method MicroED to determine the novel atomic structures of several macrocycles which have previously resisted structural determination. We show that structures of similar complexity can now be obtained rapidly from nanograms of material, and that different conformations of flexible compounds can be derived from the same experiment. These results will have impact on contemporary drug discovery as well as natural product exploration.

Identifiers

PMID37577574

DOI10.1101/2023.07.31.551405

PMCPMC10418104

What Socratic holds

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LicenceCC BY

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.