Journal article

A New Turn in Peptide-Based Imaging Agents: Foldamers Afford Improved Theranostics Targeting Cholecystokinin-2 Receptor-Positive Cancer

Alicia Corlett, Marc-Antoine Sani, Jessica Van Zuylekom, Ching-Seng Ang, Elisabeth von Guggenberg, Carleen Cullinane, Benjamin Blyth, Rodney J Hicks, Peter D Roselt, Philip E Thompson, Craig A Hutton, Mohammad B Haskali

JOURNAL OF MEDICINAL CHEMISTRY | AMER CHEMICAL SOC | Published : 2021

Abstract

Proteins adopt unique folded secondary and tertiary structures that are responsible for their remarkable biological properties. This structural complexity is key in designing efficacious peptides that can mimic the three-dimensional structure needed for biological function. In this study, we employ different chemical strategies to induce and stabilize a β-hairpin fold of peptides targeting cholecystokinin-2 receptors for theranostic application (combination of a targeted therapeutic and a diagnostic companion). The newly developed peptides exhibited enhanced folding capacity as demonstrated by circular dichroism (CD) spectroscopy, ion-mobility spectrometry-mass spectrometry, and two-dimensio..

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Grants

Awarded by Peter MacCallum Cancer Center through Peter MacCallum Cancer Foundation


Awarded by National Health and Medical Research Council (NHMRC)


Funding Acknowledgements

M.B.H. would like to dedicate this work to his grandfather, Essa Alobaidi, who recently passed away only a month after diagnosis with metastatic cancer. Essa has had the most influential impact on Dr. Haskali's academic and personal development and he had followed the progress of this work with immense interest. M.B.H. acknowledges funding from the Peter MacCallum Cancer Center through Peter MacCallum Cancer Foundation Grant #1728 and the National Health and Medical Research Council (NHMRC) for New Investigator grant funding (APP1158863). The authors acknowledge the support of the Bio21 Molecular Science and Biotechnology Institute MMSP facility and the Monash Institute of Pharmaceutical Sciences (MIPS).