"New Technologies for Accessing Modified Peptide and Proteins"

A Departmental Research Seminar

OC0.03, The Oculus, 13:00 Tuesday, 17 December 2024

Refreshment available outside OC0.03 from 12.45

Abstract

The renaissance in the use of peptides and proteins as therapeutic agents has led to significant demand for new technologies to rapidly and efficiently access these biomolecules, especially those bearing tailor-made modifications to maximize specificity and activity, or to probe biological function (e.g. through incorporation of post-translational modifications, fluorophores and/or imaging reagents).1 We have recently developed a number of synthetic and semi-synthetic technologies that enable efficient production of proteins bearing homogeneous post-translational modifications at pre-determined sites.^2,3 This talk will highlight the utility of these technologies for: (1) generating bioactive modified proteins under continuous flow conditions,³ and (2) generating proteins with site-specific and homogeneous post-translational modifications.^4-7 The talk will conclude with our efforts to employ mRNA display with genetic reprogramming to generate high affinity modified cyclic peptides for a range of therapeutic targets.^8-10

References

1 S. Kulkarni et al. Nature Rev. Chem. 2018, 2, 0122
2 S. Kulkarni et al. Nature Protocols, 2019, 14, 2229
3 L. Kambanis et al. J. Am. Chem. Soc. 2024, 146, 22027
4 B. Premdjee et al. J. Am. Chem. Soc. 2021, 143, 5336
5 S. Kulkarni et al. Angew. Chem. Int. Ed. 2022, 61, e202200163
6 L. Dowman et al. Nature Commun. 2022, 13, 6885.
7 A. Mackay et al. Angew. Chem. Int. Ed. 2023, 62, e202313037
8 J. Johansen-Leete et al. J. Am. Chem. Soc. 2020, 142, 9141
9 J. Johansen-Leete et al. Chem. Sci. 2022, 13, 3826
10 A. Norman et al. ACS Cent. Sci. 2021, 7, 1001

Biography

Richard J. Payne FAA graduated with 1st class honours in 2002 In 2003, he was awarded a Gates Scholarship to undertake his PhD at the University of Cambridge under the supervision of the late Professor Chris Abell FRS FMedSci. After his PhD, Richard moved to The Scripps Research Institute under the auspices of a Lindemann Postdoctoral Fellowship where he worked in the laboratory of Professor Chi-Huey Wong in the area of glycobiology. In 2008, he was recruited to the University of Sydney as a Lecturer of Organic within the School of Chemistry. Since 2015 he has held the position as Professor of Organic Chemistry and Chemical Biology and since 2020 has been NHMRC Leadership Fellow and Deputy Director of the ARC Centre of Excellence for Innovations in Peptide and Protein Science. Prof. Payne’s research focuses on the design and synthesis of complex biomolecules with a view to addressing important problems in biology and medicine. His lab is recognized for pioneering a number of synthetic and semi-synthetic technologies for the assembly of large polypeptides and proteins bearing post-translational modifications including glycosylation, lipidation, phosphorylation and sulfation. These methods have underpinned the discovery of modified peptide and protein drug leads for a range of diseases including anti-inflammatories, anti-thrombotics and anti-infectives. His research has been recognized by a number of awards including the Prime Minister’s Prize for Physical Scientist of the Year, HG Smith Medal, AJ Birch Medal and election as Fellow of the Australian Academy of Science.

Professor Richard J. Payne, University of Sydney