As a result of the demand for higher purity screening samples drug discovery companies today purify the majority of compound libraries prior to screening. TFA (trifluoroacetic acid) is often used in the automated purification of such compounds using LCMS. For compounds with a basic centre, TFA remains in the sample via formation of the corresponding TFA salt. This has two consequences: i. the molecular weight of the screening sample will vary depending on the number of molecules of TFA present; ii. TFA is known to contaminate certain biological assays. Therefore it is important for drug discovery companies to know which samples contain this acid, and to what degree.
Evotec OAI uses ACD/pKa Batch software to identify the samples that contain TFA by calculating acid-base ionization constants (pKa values) for thousands of compounds at a time. Evotec OAI then uses a proprietary modeling program to compare the pKa value for each atom of a compound with a working pH in order to ascertain which atoms in the molecule should be protonated and hence how many molecules of TFA will be present. The program then inserts the appropriate number of salt counter-ions into the structure representation. This allows for the calculation of the correct molecular weight so that the biologists can calculate appropriate screening quantities to facilitate the accurate measurement of biological data. This method may also be used for acids other than TFA and for basic counter-ions.
prides itself on the quality of the compounds and the supporting data that we
supply to our drug discovery partners. It is important that we do not introduce
bottlenecks within our partner's processes so we have created data management
systems that allow the efficient transfer of appropriate data to our partners.
Historically, the calculation of important physical properties for large numbers
of compounds, such as pKa, has been time-consuming. The batch pKa processing
software supplied by ACD/Labs has resolved a crucial bottleneck in this process
and allows us to rapidly calculate the pKas for thousands of compounds in a
short period of time. Our collaboration with ACD/Labs has proved very fruitful
and we are impressed by their commitment to our requirements," comments
Dr. Brian Moloney, Department Manager, Drug Discovery Services, Evotec OAI.
Dr. Robert S. DeWitte, Director of Medicinal Chemistry Solutions, ACD/Labs, adds, "Increasingly, our colleagues in pharmaceutical R&D laboratories are realizing that molecular physical properties, such as acid/base strength and solubility, have critical impact on the interpretation of experimental results. For example, if a compound is less soluble than the concentration specified in an assay protocol, the results are likely to be false negatives. In a similar manner, the presence of certain salts such as TFA salts can lead to misleading experimental information. With all the pressure on Discovery R&D, there is no room for the lost opportunity that is represented by such results. We are delighted that our customers, such as Evotec OAI, can use our technologies to add clarity to experimental results."
Advanced Chemistry Development
Development, Inc., (ACD/Labs) is a chemistry software company offering solutions
that truly integrate chemical structures with analytical chemistry information
to produce ChemAnalyticsTM. ACD/Labs creates innovative software packages that
aid chemical research scientists worldwide with spectroscopic validation of
structures, elucidation of unknown substances, chromatographic separation, medicinal
chemistry, preformulation of novel drug agents, systematic nomenclature generation,
and chemical patenting and publication. Combined, ACD/Labs' solutions create
an analytical informatics system that provides dramatic feed-forward effects
on the chemical and pharmaceutical research process. Founded in 1993, and headquartered
in Toronto, Canada, ACD/Labs employs a team of over 100 dedicated individuals
whose continual efforts carry ACD/Labs' innovative technologies into pharmaceutical,
biotech, chemical, and materials companies throughout the world. Information
about Advanced Chemistry Development and its products can be found at www.acdlabs.com.
Evotec OAI has established itself as the partner of choice for drug discovery and development services for pharmaceutical and biotechnology companies worldwide, maintaining its leadership role through innovation and unmatched customer service. The Company's business strategy is clearly focused on drug discovery. It has established the most comprehensive technology platform and skills that integrate its world-class biology and chemistry capabilities. Evotec OAI leverages this discovery engine in providing assay development and screening through to compound optimisation and drug manufacturing services to a broad and well established network of customers. In addition, the Company engages in selected discovery programs to develop drug candidates for early out-licensing. Evotec OAI's instrument and technology business is now successfully handled by its affiliate, Evotec Technologies. With over 600 people in Hamburg, Germany, and Oxfordshire, UK, Evotec OAI is dedicated to returning value to its shareholders and employees through a sustainable business strategy that balances short-term and long-term revenue opportunities. http://www.evotecoai.com.