A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules

Abed Saady; Georgia Malcolm; Matthew Fitzpatrick; Noel Pairault; Graham Tizzard; Soran Mohammed; Ali Tavassoli; Stephen Goldup

doi:10.1002/anie.202400344

A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules

Abed Saady, Georgia Malcolm, Matthew Fitzpatrick, Noel Pairault, Graham Tizzard, Soran Mohammed, Ali Tavassoli, Stephen Goldup

Chemistry

Research output: Contribution to journal › Article › peer-review

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Abstract

Inspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is “switched on” by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli. We also demonstrate that our approach is applicable to other classes of macrocycles suitable for rotaxane and catenane formation.

Original language	English
Article number	e202400344
Number of pages	7
Journal	Angewandte Chemie (International Edition)
Volume	2024
Early online date	26 Jan 2024
DOIs	https://doi.org/10.1002/anie.202400344
Publication status	Published - 6 Mar 2024

Bibliographical note

SMG thanks the ERC (Agreement no. 724987) and Leverhulme Trust (RPG-2020-399) for funding and the Royal Society for a Wolfson Research Fellowship (RSWF\FT\180010). A. Saady thanks the Council for Higher Education-Israel for a personal fellowship.

Keywords

crown ethers
macrocycles
mechanical bonds
prodrugs
rotaxanes

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10.1002/anie.202400344Licence: Creative Commons: Attribution (CC BY)

SaadyA2024PlatformFinal published version, 3 MBLicence: Creative Commons: Attribution (CC BY)

Research data supporting the publication "A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules"
Goldup, S. (Creator), University of Birmingham, 26 Jan 2024
DOI: https://doi.org/10.25500/edata.bham.00001053
Dataset

Cite this

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abstract = "Inspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is “switched on” by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli. We also demonstrate that our approach is applicable to other classes of macrocycles suitable for rotaxane and catenane formation.",

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AU - Saady, Abed

AU - Malcolm, Georgia

AU - Fitzpatrick, Matthew

AU - Pairault, Noel

AU - Tizzard, Graham

AU - Mohammed, Soran

AU - Tavassoli, Ali

AU - Goldup, Stephen

N1 - SMG thanks the ERC (Agreement no. 724987) and Leverhulme Trust (RPG-2020-399) for funding and the Royal Society for a Wolfson Research Fellowship (RSWF\FT\180010). A. Saady thanks the Council for Higher Education-Israel for a personal fellowship.

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AB - Inspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is “switched on” by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli. We also demonstrate that our approach is applicable to other classes of macrocycles suitable for rotaxane and catenane formation.

KW - crown ethers

KW - macrocycles

KW - mechanical bonds

KW - prodrugs

KW - rotaxanes

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A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules

Abstract

Bibliographical note

Keywords

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Research data supporting the publication "A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules"

Cite this