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.

Publications

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Queen AE (2020) Synthesis of [ H] and [ C]genipin. in Journal of labelled compounds & radiopharmaceuticals

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509760/1 01/10/2016 30/09/2021
1810958 Studentship EP/N509760/1 01/10/2016 31/03/2020 Adele Queen
 
Description Collaboration between Billy Kerr group at University of Strathclyde with Merck 
Organisation Merck
Department Schering Plough
Country United States 
Sector Public 
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