Date: 07-02-2025
Time: 1:00-2:00 pm
Venue: an online Zoom lecture
https://eu01web.zoom.us/meeting/register/u5ArdumsrToqGtX_zdOxsI2aOAh1B8obdaRw
Dr Anna Peacock, University of Birmingham
Title: Coiled coils as ligands for inclusion in the inorganic chemist’s toolbox
Abstract: Proteins are versatile and powerful ligands for metal ions, capable of facilitating unusual coordination chemistries and imparting unique chemical properties. These features are often challenging to replicate using small-molecule ligands, sparking significant interest in developing robust, self-assembling protein scaffolds as novel ligands for applications in inorganic chemistry. This raises the question: can artificial metal-protein complexes be designed to perform functions beyond those found in nature?
In this context, our research has focused on the development of candidate MRI contrast agents based on paramagnetic metal ions coordinated by such a class of ligands. Our ligands are peptide coiled coils, or supercoiled helices, with a hydrophobic core that can be tailored to create a metal-binding site optimized for coordination chemistry.[1] We have demonstrated that the efficiency of gadolinium(III), a metal widely used in MRI contrast agents, is significantly enhanced when complexed with our designed coiled-coil scaffold. Moreover, the performance of these complexes can be predictably tuned through de novo peptide design.[2,3]
Recently, we extended this approach to copper(II), showing that coiled-coil coordination can endow it with MRI contrast properties – something that was previously thought impossible.[4] This strategy not only makes copper(II) suitable for potential use in MRI contrast agent design, but also results in a more efficient performance compared to some current clinical agents
[1] A. F. A. Peacock, Curr. Opin. Chem. Biol., 2016, 31, 160-165.
[2] M. R. Berwick et al., J. Am. Chem. Soc., 2014, 136, 1166-1169.
[3] A. M. Webster, A. F. A. Peacock, Chem. Commun., 2021, 57, 6851-6862.
[4] A. Shah et al., Proc. Natl. Acad. Sci., USA., 2023, 120, e2219036120
Dr Sona Krajcovicova, Cambridge University
Title: Novel Synthetic Approaches for the Next-generation Therapeutics
Abstract: Next-generation therapeutics combine the potency and selectivity of biologics with the stability and delivery advantages of small molecules, enabling precise targeting of challenging biological processes. Antibody-drug conjugates (ADCs) exemplify this approach, leveraging monoclonal antibodies for the selective delivery of cytotoxic payloads to cancer cells. However, achieving homogeneity, stability, and precise drug-to-antibody ratios (DAR) remains a significant challenge. This talk highlights the rapid and efficient synthesis of next generation of tetra-divinylpyrimidine (TetraDVP) linkers for homogeneous and precise disulfide bioconjugation. Using a novel polymer-supported method, we produce TetraDVP linkers that enable precise, high-yield conjugation of payloads to antibodies. This innovative approach addresses critical challenges in ADC development, offering a scalable and versatile tool for the production of next-generation therapeutics with improved precision and efficacy in targeted cancer therapy.
