Early stage application of affinity chromatography in downstream processing is acknowledged as a desirable objective with the potential to increase yields and reduce the overall cost of goods. While protein engineering technologies are producing increasingly diverse therapeutic proteins - whole molecules, fragments, fusion proteins - advances in bioprocess development are enabling their production at industrial scale. Concomitant with these developments is an increase in the demand for sufficiently robust synthetic affinity ligands with appropriate protein binding selectivites as primary capture affinity adsorbents.

In the absence of suitable existing ligands, the development of completely new ligands has analogies with the development of novel drug compounds and the computational techniques used in the search for novel drug compounds have been adapted and used by ProMetic to inform a number of stages in the affinity ligand design process, and to gain an understanding of both the target protein and adsorbent interactions.

PBL has extensive knowledge of in silico modeling techniques, successfully applying its bioinformatics modeling suite to identify lead candidate adsorbents in a variety of projects. PBL provides customers with a range of services, from virtual screening, to the application of in silico techniques within a custom ligand discovery program:

• Screening of virtual ligand libraries. 
• Diverse or focused ligand selection from virtual 'chemical space' (Chemical Combinatorial Library CCL® ~100,000 triazine based ligands).
• Evaluating potential binding sites using structural/functional importance and blind docking 'roaming' of ligands to target protein (using crystallographic information).
• Screening designed combinatorial libraries to further explore surrounding chemical space of lead screening hits.
• Investigating the effects of support, spacer arm and surface chemistry on binding interactions by molecular dynamic modeling.

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Mr. Steve Profit has recently joined ProMetic as the EMEA and Asian sales & marketing manager. Steve has over 20 years experience in sales and marketing having previously worked in senior European and global positions for Sigma Aldrich and Millipore. Mr. Profit holds a M.Sc. Biomolecular Technology and a B.Sc. in Applied Biology.

If you would like to contact Steve with regards to any of our products or services please use the details below:

Tel: +44 (0)1223 433800

Mobile: +44 (0)7831 848644

Email: sprofit@prometicbiosciences.com

Ask Dr. Dev - What is the Difference?

Dr. Dev Baines, PBL Technical Director

Question:

Dear Dev-  Can you please provide me information on the base matrix used for ProMetic BioSciences Ltd chromatography adsorbents. What is the difference between PuraBead® 6XL and PuraBead® 6HF?

Answer-  PuraBead® is a 6% agarose bead manufactured by a novel method which does not use any organic solvents in the beading process. This provides uniform near mono-disperse beads with mean bead diameter from 90 to 100 microns.

After beading the matrix is cross-linked to provide material for derivatisation with affinity ligands.

Two different types of cross-linking chemistry are used; one to provide PuraBead® 6XL, and one to provide PuraBead® 6HF. The key difference between the cross-linking chemistries is the much higher flow rate provided by the HF cross-linking chemistry. The XL cross-linking chemistry provides very low non-specific binding and enables higher ligand densities.

Both types of PuraBead® are used to make Mimetic Blue® SA HL adsorbents including the standard Mimetic Blue® SA HL P6XL product which is widely used for purification of albumin and albumin-fusion proteins and the new Mimetic Blue® SA HL P6HF which provides the same selectivity and capacity with exceptional flow properties.

The properties of the two cross-linked base matrices are summarized below: 

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