Compound Synthesis and Analoging
The Center will work with you to design a synthetic plan meeting your research objectives. We research synthetic routes and can arrange for custom chemical synthesis of your molecular probe molecules.
We also provide access to some specialized synthesis capabilities including:
H-Cube Continuous-flow Hydrogenation Reactor. The H-Cube Continuous-flow Hydrogenation Reactor is a bench-top hydrogenation reactor, uniquely combining continuous-flow microchemistry with on-demand hydrogen generation and a disposable catalyst cartridge system. It allows fast and cost-efficient hydrogenation with superior yield when compared to conventional methods.
Microwave Assisted Synthesis. Microwave assisted synthesis is an invaluable tool within a synthesis laboratory as it often gives a purer product at higher yield than a conventional heated synthesis, and the reaction time is also in general considerably shorter. We will help you adapt your conventional protocol to a microwave enabled one.
Structure-Activity Modeling and Virtual Screening
We offer computational and analytical methods to identify the essential molecular features driving compound biological activity. Techniques employed include computer generated Macromolecule Ligand Docking, Ligand-based Virtual Screening and quantitative structure-based activity relationships, QSAR.
Computer-based Macromolecule Ligand Docking is effective in predicting the location and disposition of a small molecule in an enzyme or receptor binding site. Novel, more potent inhibitors may be designed by optimizing their fit and interaction with the active site.
For a well-characterized set of compounds, Structure-Activity Relationships may be used to predict potency and pharmacokinetic properties. SAR and QSAR provide a strong design rational and is the preferred method to drive new compound synthesis.
Ligand-based Virtual Screening uses a single compound or small set of hit compounds to build a computer-generated model of molecular features leading to biological activity. This model is then used to screen any compound library, large or small, for molecules matching those features. The top scoring “virtual hits” are then ordered from a commercial supplier or synthesized and subsequently assayed in the real screen.
Available Computational Software Packages
Ligand-based Target Identification
A large fraction of our screens are phenotypic screens where the exact molecular target is unknown. We are currently developing the capability to determine the potential biomolecular targets using the small molecules identified in a phenotypic screen.
Pharmacokinetic Prediction and Testing
Potency is irrelevant unless a compound can maintain effective concentrations inside the cell or target tissue. The Center can model a compound’s cell permeability, metabolic stability and other properties. We can also identify molecular features associated with adverse toxicological outcomes.
In addition to in silico pharmacokinetic prediction and modeling, we also serve as resource for obtaining experimental data on the measured cell permeability, plasma and liver microsome half-life, plasma protein binding, solubility and other critical pharmacokinetic characteristics.
Compound Novelty and Literature Review
Most project chemistry starts with a search of the scientific and patent literature of your hits. This information can provide guidance into the best synthetic routes, reported uses and claims surrounding your chemical matter.
Please contact Denton Hoyer (denton.hoyer@yale.edu) for an estimate of fees applicable to your project.