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Synthesis of HDAC Inhibitor Libraries via Microscale Workflow.

ABSTRACT: An integrated workflow has been established that enables the synthesis, purification, and subsequent biological testing of compound libraries on a microgram scale. This approach utilizes mass directed preparative HPLC in conjunction with charged aerosol detection (CAD) to generate solutions of investigational compounds at high purity and standardized concentrations, facilitating high fidelity biological testing. This new workflow successfully delivered libraries of histone deacetylase (HDAC) inhibitors that afforded biological data consistent with that obtained from standard scale parallel medicinal chemistry techniques. The advantages of this new approach to library synthesis include greatly reduced material requirements and amenability to high-throughput experimentation.

SUBMITTER: Dykstra KD

PROVIDER: S-EPMC7957937 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Synthesis of HDAC Inhibitor Libraries via Microscale Workflow.

Dykstra Kevin D KD Streckfuss Eric E Liu Min M Liu Jian J Yu Younong Y Wang Ming M Kozlowski Joseph A JA Myers Robert W RW Buevich Alexei V AV Maletic Milana M MM Vachal Petr P Krska Shane W SW

ACS medicinal chemistry letters 20210208 3

An integrated workflow has been established that enables the synthesis, purification, and subsequent biological testing of compound libraries on a microgram scale. This approach utilizes mass directed preparative HPLC in conjunction with charged aerosol detection (CAD) to generate solutions of investigational compounds at high purity and standardized concentrations, facilitating high fidelity biological testing. This new workflow successfully delivered libraries of histone deacetylase (HDAC) inh ...[more]

PMID: 33738059

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