CLC Milstein Chemistry Core Facility

Services

  • Chemical synthesis services
    • For compounds that are not readily available
    • For assay development tools and reagents
    • For compounds for in vitro and in vivo assays
    • For large-scale chemical synthesis of compounds
    • For confirmatory synthesis of compounds
  • Chemical analysis services
    • Structure-activity relationship studies on pharmacophores
    • Structure determination of unknown molecular entities
    • Chemical analysis of reaction mixtures, extracts and bioassays
    • Molecular modeling and in silico screening
  • Consultation
  • Seminars, workshops and training

Summary

The WCM CLC Milstein Chemistry Core Facility provides state-of-the-art chemical synthesis and analysis resources and services, and expertise in their applications, to the WCM community and to outside investigators. Services include (1) chemical synthesis for compounds that are not readily available, for assay development tools and reagents, for compounds for in vitro and in vivo assays, for large-scale chemical synthesis of compounds, and for confirmatory synthesis of compounds; and (2) chemical analysis for structure-activity relationship studies on pharmacophores, for structure determination of unknown molecular entities, for chemical analysis of reaction mixtures, cell extracts and bioassays, and for molecular modeling and in silico screening. The core facility provides consultation on project design and data analysis, and offers seminars, training and educational workshops.

Overview

History: The Abby and Howard P. Milstein Chemistry Core Facility (MCCF) was founded in 2006 with generous support from the Howard and Abby Milstein Foundation. The core became part of the WCM Core Laboratories Center (CLC) in 2015.

Location: The Milstein Chemistry Core Facility is located on the 16th floor of the Belfer Research Building at 413 East 69th Street, New York, NY. The core is near both the Tri-Institutional Therapeutics Discovery Institute (Tri-I TDI) and the WCM Molecular Imaging Innovations Institute (MI3). This facilitates productive sharing of reagents, instruments, knowledge and expertise, and allows for collaborative interactions with researchers interested in drug discovery and molecular imaging.

WCM Core Laboratories Center (CLC): The WCM CLC was established in 2015. The CLC includes core facilities that offer resources and services in genomics and epigenomics, proteomics and metabolomics, flow cytometry, imaging (e.g., optical and electron microscopy, high content screening, MRI, PET/CT, and ultrasound), synthetic and analytical chemistry, and nuclear magnetic resonance (NMR).

Open to all: The resources and services of the core facility are open to all investigators at Weill Cornell Medicine, Cornell University and Cornell-affiliated institutions. The facility also provides services to external investigators at both academic institutions and commercial enterprises.

Services:

Chemical synthesis: Services include synthesis of single compounds that are known in the literature, or have been obtained from a chemical screen, and synthesis of compounds with unknown utility, but are predicted to have desirable properties. Synthesis of assay development tools and reagents including: fluorescently labeled compounds; affinity labeled compounds; cross linker-tethered molecules; labeled (13C, 2H, 15N) and radiolabeled (3H, 14C, 32P, 125I, etc.) compounds for preclinical and clinical pharmacological studies, which cannot be directly addressed by the WCM CLC Citigroup Biomedical Imaging Center (CBIC). Synthesis of compounds in quantities that allow for in vitro and in vivo assays, and follow-up assays, when warranted. Large-scale chemical synthesis of compounds with demonstrated biological activity in primary assays, to provide material for further investigation. Confirmatory synthesis of compounds identified via high-throughput screening. Structure-activity relationship (SAR) studies on validated pharmacophores in order to optimize targeting, specificity, and bioavailability, while minimizing toxicity.

Chemical analysis: Services include identification of unknown and/or known molecular entities, evaluation of and/or purification of chemical reaction mixtures, evaluation of extracts from cellular assays, analysis of biological extracts, serum, or plasma.

RapidFire High Throughput Screening: The RapidFire unit is a micro-scale solid-phase extraction (SPE) based, front-end instrument that enables detection of native compounds by mass spectrometry. Requiring no labels or surrogates, it enables the screening of intractable or challenging targets that are not amenable to fluorescence or luminescence. Sample throughput is 10x faster than conventional LC/MS screening methods.

Data Analysis and Project Development: Molecular modeling and in silico screening using a variety of computational tools, including the Schrödinger software suite and Chemical Computing Group's Molecular Operating Environment (MOE).

Consultation: Consultation on synthetic, medicinal, and analytical chemistry applications, including: project design, molecular modeling, in silico library screening, sample preparation, data collection methods, and data analysis.

Resources

The core’s resources include four chemical fume hoods, a CEM-Discover microwave irradiator with 48-position autosampler, a Labconco FreeZone Plus 6 liter lyophilizer, as well as a full array of analytical and preparative scale instrumentation, including: Waters ACQUITY SQD UPLC/MS (PDA, fluorescence, and mass detection, up to 2000 amu); Varian preparative HPLC with PDA detection; Varian 4000 GC-MS (internal, external and hybrid ionization); Bruker TENSOR 27 series FT-IR spectrometer equipped with a Diamond ATR; and four ISCO CombiFlash Rf automated chromatography units.

The core has access to resources in the Tri-I TDI, including: Waters ACQUITY I-Class UPLC/MS (PDA, fluorescence, and mass detection, up to 3000 amu); Waters ACQUITY H-Class UPLC/MS (PDA, and mass detection, up to 1250 amu); and Waters Autopure prep HPLC/MS (PDA, evaporative light scattering, and mass detection, up to 3000 amu).

The core also has access to an Agilent RapidFire high-throughput MS system located in the nearby WCM CLC/MCC Proteomics and Metabolomics Core Facility, and to the NMR instruments located in the nearby WCM CLC NMR Core Facility.

Links To More Information

For more information about services and pricing, to register as a user of the core, to submit samples, to schedule time on the instruments, and/or to arrange for training, please go to the WCM iLab portal.

Contact Information

J. David Warren, Ph.D.,
Core Director, CLC Milstein Chemistry Core Facility
(646) 962-6138
jdwarren@med.cornell.edu