Novel Strategy for Non-Aqueous Bioconjugation of Substituted Phenyl-1,2,4-triazole-3,5-dione Analogues.

Hiscocks, HG; Ung, AT; Pascali, G

Novel Strategy for Non-Aqueous Bioconjugation of Substituted Phenyl-1,2,4-triazole-3,5-dione Analogues.

Hiscocks, HG Ung, AT Pascali, G

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Molecules, 2022, 27, (19), pp. 6667
Issue Date:: 2022-10-07

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Field	Value	Language
dc.contributor.author	Hiscocks, HG
dc.contributor.author	Ung, AT
dc.contributor.author	Pascali, G
dc.date.accessioned	2022-10-31T01:13:00Z
dc.date.available	2022-10-03
dc.date.available	2022-10-31T01:13:00Z
dc.date.issued	2022-10-07
dc.identifier.citation	Molecules, 2022, 27, (19), pp. 6667
dc.identifier.issn	1420-3049
dc.identifier.issn	1420-3049
dc.identifier.uri	http://hdl.handle.net/10453/163015
dc.description.abstract	A novel 4-[4-(pentafluoro-λ⁶-sulfanyl)phenyl]-1,2,4-triazole-3,5-dione (5a) was synthesised as a potential [18F]radio-prosthetic group for radiolabelling peptides and proteins via selective bioconjugation with the phenolic side chains of tyrosine residues. Preliminary conjugation tests revealed the rapid hydrolysis of 5a under semi-aqueous conditions; these results led to further investigation into the electronic substituent effects of PTAD derivatives and corresponding hydrolytic stabilities. Five derivatives of 5a with para substituents of varying electron donating and withdrawing effects were synthesised for the investigation. The bioconjugation of these derivatives with model tyrosine was monitored in both aqueous and organic media in the presence of a variety of catalysts. From these investigations, we have found HFIP to be an effective catalyst when used in tandem with DCM as a solvent to give PTAD-tyrosine conjugate products (6a-f) in satisfactory to good yields (54-79%), whereas analogous reactions performed in acetonitrile were unsuccessful. The discovery of this system has allowed for the successful conjugation of electron-deficient PTAD derivatives to tyrosine, which would otherwise be unachievable under aqueous reaction conditions. The inclusion of these electron-deficient, fluorinated PTAD derivatives for use in the PTAD-tyrosine conjugation will hopefully broaden their applicability within fields such as 19F-MRI and PET imaging.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	Molecules
dc.relation.isbasedon	10.3390/molecules27196667
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0307 Theoretical and Computational Chemistry
dc.subject.classification	Organic Chemistry
dc.subject.mesh	Acetonitriles
dc.subject.mesh	Peptides
dc.subject.mesh	Solvents
dc.subject.mesh	Triazoles
dc.subject.mesh	Tyrosine
dc.subject.mesh	Acetonitriles
dc.subject.mesh	Triazoles
dc.subject.mesh	Tyrosine
dc.subject.mesh	Peptides
dc.subject.mesh	Solvents
dc.title	Novel Strategy for Non-Aqueous Bioconjugation of Substituted Phenyl-1,2,4-triazole-3,5-dione Analogues.
dc.type	Journal Article
utslib.citation.volume	27
utslib.location.activity	Switzerland
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0305 Organic Chemistry
utslib.for	0307 Theoretical and Computational Chemistry
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-10-31T01:12:57Z
pubs.issue	19
pubs.publication-status	Published online
pubs.volume	27
utslib.citation.issue	19

Abstract:

A novel 4-[4-(pentafluoro-λ⁶-sulfanyl)phenyl]-1,2,4-triazole-3,5-dione (5a) was synthesised as a potential [18F]radio-prosthetic group for radiolabelling peptides and proteins via selective bioconjugation with the phenolic side chains of tyrosine residues. Preliminary conjugation tests revealed the rapid hydrolysis of 5a under semi-aqueous conditions; these results led to further investigation into the electronic substituent effects of PTAD derivatives and corresponding hydrolytic stabilities. Five derivatives of 5a with para substituents of varying electron donating and withdrawing effects were synthesised for the investigation. The bioconjugation of these derivatives with model tyrosine was monitored in both aqueous and organic media in the presence of a variety of catalysts. From these investigations, we have found HFIP to be an effective catalyst when used in tandem with DCM as a solvent to give PTAD-tyrosine conjugate products (6a-f) in satisfactory to good yields (54-79%), whereas analogous reactions performed in acetonitrile were unsuccessful. The discovery of this system has allowed for the successful conjugation of electron-deficient PTAD derivatives to tyrosine, which would otherwise be unachievable under aqueous reaction conditions. The inclusion of these electron-deficient, fluorinated PTAD derivatives for use in the PTAD-tyrosine conjugation will hopefully broaden their applicability within fields such as 19F-MRI and PET imaging.

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http://hdl.handle.net/10453/163015