Is it really cost effective to develop a custom affinity ligand as a capture step in your downstream process?

June 13, 2017 Andy Davies

One issue that is often of concern to many process development scientists is the limited time available to develop purification processes. This can restrict their choice of chromatography resins to those they’ve used before or are readily available in the hope that they will give the selectivity required and provide the final purity needed when used in combination with several other resins. However, this can lead to sub-optimal separation and multi-step processes which in turn make for a less cost-effective process.

Equally it’s apparent that the purification challenges are becoming more complex and the need for higher selectivity and capacity ever increase.

At Prometic Bioseparations Ltd (PBL) we have been pioneering design, development and manufacture of affinity purification technology for lab-scale and industrial-scale bioprocessing since 1987 and now have over 30 years’ experience in the development of affinity products and design of new custom adsorbents.

We offer an extensive range of off-the-shelf Bioseparation products for the recovery and purification of biologicals as well as purification services including bespoke custom designed chromatography adsorbents, process development and in silico modelling applications.

We understand that early stage application of affinity chromatography in downstream processing is very advantageous 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. Along with these developments is an increase in the demand for sufficiently robust synthetic affinity ligands with appropriate protein binding selectivity’s 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.

We have extensive knowledge of in silico modelling techniques, successfully applying its bioinformatics modelling suite to identify lead candidate adsorbents in a variety of projects. We can provide you 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 modelling.

Whilst the above approach can give rise to a very selective affinity adsorbent, if time is a major consideration, we have now made available a Multi-Mode Mimetic Ligand ™ Library which provides a diverse library of 96 ligands which can be used to 'short-cut' the above ligand development programme. So now you can perform the initial phase of screening in house speeding up the ligand selection and also avoiding the need for potential protracted contractual discussions.

 

To find out more about the Multi-Mode Mimetic Ligand™ library please follow this LINK.

 

All trademarks, trade names, trade dress, product names and logos appearing on this website are the property of Prometic Bioseparations Ltd.

 

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