A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation

The synthesis of artificial sequence-defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapter...

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Main Authors: Frommer, J, Oppenheimer, R, Allott, BM, Núñez-Pertíñez, S, Wilks, TR, Cox, LR, Bath, J, O'Reilly, RK, Turberfield, AJ
Format: Journal article
Language:English
Published: Wiley 2024
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author Frommer, J
Oppenheimer, R
Allott, BM
Núñez-Pertíñez, S
Wilks, TR
Cox, LR
Bath, J
O'Reilly, RK
Turberfield, AJ
author_facet Frommer, J
Oppenheimer, R
Allott, BM
Núñez-Pertíñez, S
Wilks, TR
Cox, LR
Bath, J
O'Reilly, RK
Turberfield, AJ
author_sort Frommer, J
collection OXFORD
description The synthesis of artificial sequence-defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA-templated reactions. Here, we report an architecture for DNA-templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA-templated reaction. This protective effect has the potential to overcome the challenges associated with programmable sequence-controlled synthesis of long non-natural polymers by extending the lifetime of the reactive building blocks.
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spelling oxford-uuid:144b5eab-2cf5-42a9-b4d1-7b7577ae82bb2024-05-13T10:09:12ZA new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:144b5eab-2cf5-42a9-b4d1-7b7577ae82bbEnglishSymplectic ElementsWiley2024Frommer, JOppenheimer, RAllott, BMNúñez-Pertíñez, SWilks, TRCox, LRBath, JO'Reilly, RKTurberfield, AJThe synthesis of artificial sequence-defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA-templated reactions. Here, we report an architecture for DNA-templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA-templated reaction. This protective effect has the potential to overcome the challenges associated with programmable sequence-controlled synthesis of long non-natural polymers by extending the lifetime of the reactive building blocks.
spellingShingle Frommer, J
Oppenheimer, R
Allott, BM
Núñez-Pertíñez, S
Wilks, TR
Cox, LR
Bath, J
O'Reilly, RK
Turberfield, AJ
A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation
title A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation
title_full A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation
title_fullStr A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation
title_full_unstemmed A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation
title_short A new architecture for DNA-templated synthesis in which abasic sites protect reactants from degradation
title_sort new architecture for dna templated synthesis in which abasic sites protect reactants from degradation
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