Journal article

Modular Synthesis of Trifunctional Peptide-oligonucleotide Conjugates via Native Chemical Ligation

Mohadeseh Dastpeyman, John A Karas, Azin Amin, Bradley J Turner, Fazel Shabanpoor

Frontiers in Chemistry | FRONTIERS MEDIA SA | Published : 2021

Abstract

Cell penetrating peptides (CPPs) are being increasingly used as efficient vectors for intracellular delivery of biologically active agents, such as therapeutic antisense oligonucleotides (ASOs). Unfortunately, ASOs have poor cell membrane permeability. The conjugation of ASOs to CPPs have been shown to significantly improve their cellular permeability and therapeutic efficacy. CPPs are often covalently conjugated to ASOs through a variety of chemical linkages. Most of the reported approaches for ligation of CPPs to ASOs relies on methodologies that forms non-native bond due to incompatibility with in-solution phase conjugation. These approaches have low efficiency and poor yields. Therefore,..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council


Awarded by Bethlehem Griffith Research Foundation scholarship


Awarded by FightMND Mid-career Fellowship


Awarded by NHMRC-ARC Dementia Research Leadership Fellowship


Funding Acknowledgements

This work was supported by National Health and Medical Research Council (Project Grants 1138033 to FS and BT). AA is a recipient of Bethlehem Griffith Research Foundation scholarship (1808). FS is a recipient of FightMND Mid-career Fellowship (04MCR). BT is a recipient of NHMRC-ARC Dementia Research Leadership Fellowship (1137024) and Stafford Fox Medical Research Foundation Grant.