Optimisation of sortase-mediated protein labelling as a tool for biotechnology and pharmaceutical development
Lead Research Organisation:
University of Leeds
Department Name: Sch of Chemistry
Abstract
Labelling of proteins is fundamental to laboratory investigations and industrial applications such as the development of diagnostics. The market for protein labelling reagents is worth approximately $2bn a year and new innovations which increase the efficiency of protein labelling and reduce the cost of this process are always needed. In this project, we are developing a new protocol for the use of sortase in protein labelling. This technology has the potential to allow the rapid (<1 hour) generation of homogenously modified proteins with minimal excess reagent and small quantities of the labelling protein. During the project we will investigate a range of potential commercial applications including the potential of the technology for application in the generation of modified antibodies, which represent a major new class of anti-cancer drugs.
Publications
Dolan JP
(2022)
Synthesis of cholera toxin B subunit glycoconjugates using site-specific orthogonal oxime and sortase ligation reactions.
in Frontiers in chemistry
Morgan HE
(2022)
Combined Application of Orthogonal Sortases and Depsipeptide Substrates for Dual Protein Labeling.
in Bioconjugate chemistry
Morgan HE
(2022)
Challenges in the use of sortase and other peptide ligases for site-specific protein modification.
in Chemical Society reviews
| Description | In this proposal we continued the development of a protein labelling technology to proof-of-concept stage. Through this project we demonstrated the full scope of the technology and obtained key data that is vital for intellectual property purposes. We have now shown successful high-yielding reaction on several different protein systems and have identified key parameters required for optimisation as well as identifying the key conditions required for successful labelling of proteins. We are now moving to the next phase of the project to identify mechanisms to exploit the results of the project most effectively by collaboration with a targeted industrial partner using internal UoL funding to facilitate this interaciton. This evaluation is still ongoing having been delayed due to the COVID-19 pandemic. |
| Exploitation Route | Prior to publication, we are investigating patent protection of the technology. After this point we anticipate that the technology could be adapted for application in industry or in an academic setting. |
| Sectors | Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | The technology developed through this proposal is now being used in industrial collaborations with existing and prospective non-academic research partners. Details of these collaborations are currently confidential. |
| First Year Of Impact | 2019 |
| Sector | Chemicals,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | BBSRC follow-on fund |
| Amount | £250,000 (GBP) |
| Funding ID | BB/R005540/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 09/2019 |
| Description | Multivalent display of sugar antigens via site selective enzymatic modification of cholera toxin |
| Amount | £112,000 (GBP) |
| Organisation | GlaxoSmithKline (GSK) |
| Sector | Private |
| Country | Global |
| Start | 10/2020 |
| End | 09/2024 |
| Description | Sortase conjugate vaccines |
| Amount | £39,288 (GBP) |
| Organisation | University of Leeds |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2019 |
| End | 03/2020 |