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Large, Dynamic Capsules for Biomolecular Cargoes

Objective

Recent years have seen the discovery and development of progressively larger soluble metal-organic capsules. Although the largest of these now possess sufficiently large volumes to accommodate small proteins and other biomacromolecules, the structures of the largest capsules so far reported are inherently porous, which means that binding cargoes inside requires covalent tethering to the cage framework. This requirement limits the range of potential guest species and alters their conformations. This project will build upon our successes in binding small biomolecules, and our recent preparation of larger, enclosed cages, to prepare novel capsules that will be the largest discrete such structures yet prepared. These cages will be designed to possess three key features to enable the encapsulation of a wide range of biomolecules. Firstly, they will be designed to be soluble and stable in water. Secondly, they will possess a sufficient degree of surface enclosure to enable extensive contact between cage panels and lipophilic biomolecule surfaces. Thirdly, complementary charges and specific interactions will be built into capsule interiors, with specific biomolecular targets in mind. New mechanisms will be developed for the capsule interiors to dynamically adapt, enabling them to optimize their inner surfaces for binding to a specific cargo, and to reversibly shrink and expand, allowing cargoes to be bound and ejected as part of a chemical purification cycle. Encapsulated proteins will not have a preferred surface orientation, potentially enabling their structures to be solved using cryo-EM. Our tightly woven capsules may enable enzymes to function under conditions where they may not ordinarily be soluble or active. The knotted topologies of some of our targets, which will enable them to expand and shrink reversibly, will also be the most complex yet prepared synthetically.

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Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-ADG

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution
€ 2 004 236,25
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom
Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost
No data

Beneficiaries (2)