Enabling next-generation antibody-based therapeutics and diagnostics
Lead Research Organisation:
University College London
Department Name: Chemistry
Abstract
There is a clear need for Organic Chemists to contribute to the field of Biology through the conduit of Chemical Biology. This project will work with Dr Vijay Chudasama, along with Dr James Baker and MRC Technology to aid in providing significant steps in this direction via the creation of therapeutics generated by site-specific protein modification. The project will be based on using core synthetic organic chemistry to deliver entities that will meet the needs of forming the next-generation of antibody-based therapeutics. In the area of site-selective protein modification, we are at the centre of developing a ground-breaking technology based on the insertion of small molecules bearing reactive handles into native disulfide bonds and cysteines. Our strategy has been well received in the literature (e.g. Nature Chem., 2016, 8, 114; Chem. Sci., 2016, 7, 799; Nature Commun., 2015, 6, 6645; Chem. Commun., 2015, 51, 15304; Chem. Commun., 2015, 51, 10624; Org. Biomol. Chem., 2015, 13, 7946; Bioconjugate Chem., 2014, 25, 611; Org. Biomol. Chem., 2014, 12, 557; Chem. Commun., 2013, 49, 8187; Org. Biomol. Chem., 2013, 11, 2408; Chem. Commun., 2011, 47, 8781) and we hope to continue to publish greatly in this area. With our experience, interesting challenges in the modification of certain peptides and proteins have arisen. This project creates the opportunity to contribute to this area and make a significant impact to the field of Chemical Biology.
People |
ORCID iD |
Vijay Chudasama (Primary Supervisor) | |
Calise Bahou (Student) |
Publications
Bahou C
(2019)
Use of pyridazinediones as extracellular cleavable linkers through reversible cysteine conjugation.
in Chemical communications (Cambridge, England)
Bahou C
(2018)
Highly homogeneous antibody modification through optimisation of the synthesis and conjugation of functionalised dibromopyridazinediones.
in Organic & biomolecular chemistry
Bahou C
(2019)
Disulfide Modified IgG1: An Investigation of Biophysical Profile and Clinically Relevant Fc Interactions
in Bioconjugate Chemistry
Sadraeian M
(2020)
Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells.
in International journal of molecular sciences
Szijj PA
(2018)
Minireview: Addressing the retro-Michael instability of maleimide bioconjugates.
in Drug discovery today. Technologies
Wall A
(2020)
One-pot thiol-amine bioconjugation to maleimides: simultaneous stabilisation and dual functionalisation.
in Chemical science
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509577/1 | 01/10/2016 | 24/03/2022 | |||
1785286 | Studentship | EP/N509577/1 | 01/10/2016 | 31/03/2021 | Calise Bahou |
Description | 1. Discovered novel synthesis for disulfide modification reagents - pyridazinediones 2. Discovered optimal conjugation conditions for forming natively rebridged IgG1 antibodies. 3. Explored impact of disulfide modification on IgG1 model antibodies Fc function. Study also applies to wider antibody function. 4. Discovered a linker capable of slow extracellular release of cargo. |
Exploitation Route | Other research groups, or scientists in industry may decide to implement these findings in ADC synthesis and rational ADC design. |
Sectors | Chemicals,Healthcare,Manufacturing, including Industrial Biotechology |
URL | https://pubs.rsc.org/en/content/articlelanding/2018/ob/c7ob03138f#!divAbstract |