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Article: Guanidine Additive Enabled Intermolecular ortho-Phthalaldehyde-Amine-Thiol Three-Component Reactions for Modular Constructions

TitleGuanidine Additive Enabled Intermolecular ortho-Phthalaldehyde-Amine-Thiol Three-Component Reactions for Modular Constructions
Authors
KeywordsChemoselectivity
Drug Conjugation
Isoindoles
Ortho-Phthalaldehyde
Peptide Conjugation
Issue Date31-Jan-2023
PublisherWiley
Citation
Angewandte Chemie International Edition, 2023, v. 62, n. 10 How to Cite?
Abstract

Recently, ortho-phthalaldehyde (OPA) is experiencing a renascence for the modification of
proteins and peptides through OPA-amine two-component reactions for bioconjugation and intramolecular
OPA-amine-thiol three-component reactions for cyclization. Historically, small thiol molecules were used in
large excess to allow for the intermolecular OPA-aminethiol reaction forming 1-thio-isoindole derivatives. In
this study, we discovered that guanidine could serve as an effective additive to switch the intermolecular OPA-amine-thiol three-component reaction to a stoichiometric process and enable the modular construction of peptide-peptide, and peptide-drug conjugate structures. Thus, 12 model peptide-peptide conjugates have been synthesized from unprotected peptides featuring all proteinogenic residues. Besides, 6 peptide-drug conjugates have been prepared in one step, with excellent conversions and isolated yields. In addition, a conjugate product has been further functionalized by utilizing a premodified OPA derivative, demonstrating the versatility and flexibility of this reaction.


Persistent Identifierhttp://hdl.handle.net/10722/331194
ISSN
2023 Impact Factor: 16.1
2023 SCImago Journal Rankings: 5.300
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, CHP-
dc.contributor.authorChong, TH-
dc.contributor.authorWei, TY-
dc.contributor.authorLiu, H-
dc.contributor.authorLi, XC-
dc.date.accessioned2023-09-21T06:53:35Z-
dc.date.available2023-09-21T06:53:35Z-
dc.date.issued2023-01-31-
dc.identifier.citationAngewandte Chemie International Edition, 2023, v. 62, n. 10-
dc.identifier.issn1433-7851-
dc.identifier.urihttp://hdl.handle.net/10722/331194-
dc.description.abstract<p>Recently, ortho-phthalaldehyde (OPA) is experiencing a renascence for the modification of<br>proteins and peptides through OPA-amine two-component reactions for bioconjugation and intramolecular<br>OPA-amine-thiol three-component reactions for cyclization. Historically, small thiol molecules were used in<br>large excess to allow for the intermolecular OPA-aminethiol reaction forming 1-thio-isoindole derivatives. In<br>this study, we discovered that guanidine could serve as an effective additive to switch the intermolecular OPA-amine-thiol three-component reaction to a stoichiometric process and enable the modular construction of peptide-peptide, and peptide-drug conjugate structures. Thus, 12 model peptide-peptide conjugates have been synthesized from unprotected peptides featuring all proteinogenic residues. Besides, 6 peptide-drug conjugates have been prepared in one step, with excellent conversions and isolated yields. In addition, a conjugate product has been further functionalized by utilizing a premodified OPA derivative, demonstrating the versatility and flexibility of this reaction.<br></p>-
dc.languageeng-
dc.publisherWiley-
dc.relation.ispartofAngewandte Chemie International Edition-
dc.subjectChemoselectivity-
dc.subjectDrug Conjugation-
dc.subjectIsoindoles-
dc.subjectOrtho-Phthalaldehyde-
dc.subjectPeptide Conjugation-
dc.titleGuanidine Additive Enabled Intermolecular ortho-Phthalaldehyde-Amine-Thiol Three-Component Reactions for Modular Constructions-
dc.typeArticle-
dc.identifier.doi10.1002/anie.202217150-
dc.identifier.scopuseid_2-s2.0-85146969816-
dc.identifier.volume62-
dc.identifier.issue10-
dc.identifier.eissn1521-3773-
dc.identifier.isiWOS:000922341800001-
dc.identifier.issnl1433-7851-

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