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

Abed Saady; Georgia K. Malcolm; Matthew P. Fitzpatrick; Noel Pairault; Graham J. Tizzard; Soran Mohammed; Ali Tavassoli; Stephen M. Goldup

doi:10.1002/anie.202400344

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

Abed Saady
, Georgia K. Malcolm
, Matthew P. Fitzpatrick
, Noel Pairault
, Graham J. Tizzard
, Soran Mohammed
, Ali Tavassoli
, Stephen M. Goldup

University of Birmingham
University of Southampton

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

12 Scopus citations

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
Journal	Angewandte Chemie - International Edition
Volume	63
Issue number	16
Early online date	26 Jan 2024
DOIs	https://doi.org/10.1002/anie.202400344
State	Published - 15 Apr 2024
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Funding

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.

Funders	Funder number
Leverhulme Trust	RPG‐2020‐399
Royal Society	RSWF\FT\180010
European Commission	724987
Council for Higher Education

Keywords

crown ethers
macrocycles
mechanical bonds
prodrugs
rotaxanes

Access to Document

10.1002/anie.202400344

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 - Mohammed, Soran

AU - Tavassoli, Ali

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

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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