Purpose
The primary purpose of the Chemical Biology Core (CBC) is to assist, identify and optimize chemical probes and new lead compounds that may benefit both biochemical mechanistic studies and drug discovery & development, which will ultimately provide therapeutic benefit to cancer patients. The shared resource comprises 2 functional units (Chemistry and Structural Biology) that work together to provide complementary and iterative approaches for identifying novel anti-cancer agents.
Services
- Production of functional proteins of crystallization-grade purity in mg quantities for biochemical and biophysical studies; services include all steps from construct design to purification of homogenous protein.
- Crystallizing proteins, protein-small molecule complexes, protein-protein complexes, or protein-DNA complexes, and determine their 3-dimensional structure using macromolecular X-ray crystallography.
- Studying the thermodynamics (stoichiometry, KD, ΔH, ΔS) of protein-ligand interactions using Isothermal Titration Calorimetry (ITC).
- Studying the aggregation of small molecules and proteins using Dynamic Light Scattering (DLS).
- Common instrumentation; including robotics and plate readers for screening purposes.
- Synthesis: Re-synthesis of hits and leads to confirm structure and purity; medicinal chemistry and focused library design and synthesis for structure-activity relationships & lead optimization, synthesis of difficult-to-obtain probes/drugs for proof-of-principle studies, synthesis of biotynylated compounds/probes for chemical proteomics studies, multi-gram scale synthesis of potent compounds for pre-clinical in vivo studies.
- Pro-Drug synthesis and salt formation of potent compounds for preclinical studies.
- Analytical chemistry, solubility and stability assessments for lead compounds that are used for in vivo studies.
- Nuclear Magnetic Resonance (NMR), Mass Spectrometers (HPLC-MS and TOF-LCMS) instrumentation.
Location
The Chemical Biology Core, Chemistry Section, is located in the Moffitt Research Center (MRC) on the fourth floor, room 4017. The Structural Biology Section is located in the Stabile Research Building (SRB) on the fourth floor, room 24208.
Scheduling
The BC uses a Laboratory Information Management Suite (LIMS) located on the Moffittnet for billing and usage tracking.
Publications
All publications based on work conducted in the Chemical Biology Core should acknowledge the facility. A suggested statement is as follows:
If a Core Staff member(s) significantly contributes or participates in a project, investigators are encouraged to consider including the individual(s) in the list of authors.
Contacts
Scientific Directors
Harshani Lawrence, PhD
harshani.lawrence@moffitt.org
Office: 813-745-6076
Ernst Schonbrunn, PhD
ernst.schonbrunn@moffitt.org
Office: 813-745-4703
Staff Scientist
Andreas Becker, PhD
andreas.becker@moffitt.org
Office: 813-745-5461
This work has been supported in part by the Chemical Biology Core at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute and funded in part by Moffitt’s Cancer Center Support Grant (P30-CA076292)