Enhanced Iridium Complexes for Elevated Substrate Applicability in Isotope Labelling Processes
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
The preparation of complex 3H- and 2H-labelled peptides and proteins is currently a major challenge for existing isotope labelling methodology. The demand for 3H- and 2H-labelled peptides and proteins for biological assay development, and in vitro and in vivo metabolism studies have significantly increased as pharmaceutical companies increasingly target biologics as new medicines. Traditionally, these labelled peptides are prepared via a palladium-catalysed tritium gas reduction of iodotyrosine- or dehydroleucine-containing analogues. These methods, however, suffer from two main drawbacks. Firstly, precursor peptide or protein synthesis is required, which can be practically challenging and cost intensive. Secondly, once the precursor peptide has been obtained, it may contain amino acids that are not compatible with the reduction conditions, which often leads to reaction failure.
In this research project, a suite of iridium(I) catalysts will be developed to promote sp3 C-H bond exchange, initially using simple -amino acids as substrates to guide catalyst development. Following these extensive studies on amino acids, the work will be extended to the labelling of peptides and proteins. It is planned to apply active catalysts to the tritium labelling of peptides and proteins that are of direct interest in supporting the industrial collaborator's biologics pipeline.
In this research project, a suite of iridium(I) catalysts will be developed to promote sp3 C-H bond exchange, initially using simple -amino acids as substrates to guide catalyst development. Following these extensive studies on amino acids, the work will be extended to the labelling of peptides and proteins. It is planned to apply active catalysts to the tritium labelling of peptides and proteins that are of direct interest in supporting the industrial collaborator's biologics pipeline.
People |
ORCID iD |
William Kerr (Primary Supervisor) | |
Adele Queen (Student) |
Publications
Queen AE
(2020)
Synthesis of [3 H] and [14 C]genipin.
in Journal of labelled compounds & radiopharmaceuticals
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509760/1 | 30/09/2016 | 29/09/2021 | |||
1810958 | Studentship | EP/N509760/1 | 30/09/2016 | 30/03/2020 | Adele Queen |
Description | Collaboration between Billy Kerr group at University of Strathclyde with Merck |
Organisation | Merck |
Department | Schering Plough |
Country | United States |
Sector | Private |
PI Contribution | Active laboratory research has been undertaken at Strathclyde, with regular updates given to Merck collborators, |
Collaborator Contribution | Regularly contribute to update meetings with ideas and suggestions. Support in synthesis of more elaborate materials. |
Impact | N/A |
Start Year | 2016 |
Description | University of Strathclyde (William Kerr group) and RTI International. |
Organisation | RTI International |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | Significant impact was made by the University of Strathclyde by employing our groups catalysts to real life industry problems within RTI international's radio labelling department. Our iridium catalysts were used to effectively introduce heavy isotopes of hydrogen to interesting drug molecules which were required for DMPK metabolism studies at RTI. |
Collaborator Contribution | RTI provided significant contribution to the University of Strathclyde by hosting the student for the summer. Scientists at RTI shared skills and expertise and trained the student in the handling of radioactive material (something which could not be achieved or experienced at Strathclyde), expanding the students practical repertoire. |
Impact | Publication of the work carried out at RTI in Journal Labelled Compound Radiopharm https://doi.org/10.1002/jlcr.3832 |
Start Year | 2019 |