Peptide Ligation at High Dilution via Reductive Diselenide-Selenoester Ligation.

Chisholm, TS; Kulkarni, SS; Hossain, KR; Cornelius, F; Clarke, RJ; Payne, RJ

Peptide Ligation at High Dilution via Reductive Diselenide-Selenoester Ligation.

Chisholm, TS Kulkarni, SS Hossain, KR Cornelius, F Clarke, RJ Payne, RJ

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Publisher:: AMER CHEMICAL SOC
Publication Type:: Journal Article
Citation:: Journal of the American Chemical Society, 2020, 142, (2), pp. 1090-1100
Issue Date:: 2020-01

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Field	Value	Language
dc.contributor.author	Chisholm, TS
dc.contributor.author	Kulkarni, SS
dc.contributor.author	Hossain, KR
dc.contributor.author	Cornelius, F
dc.contributor.author	Clarke, RJ
dc.contributor.author	Payne, RJ
dc.date.accessioned	2021-03-12T03:26:23Z
dc.date.available	2021-03-12T03:26:23Z
dc.date.issued	2020-01
dc.identifier.citation	Journal of the American Chemical Society, 2020, 142, (2), pp. 1090-1100
dc.identifier.issn	0002-7863
dc.identifier.issn	1520-5126
dc.identifier.uri	http://hdl.handle.net/10453/147060
dc.description.abstract	Peptide ligation chemistry has revolutionized protein science by providing access to homogeneously modified peptides and proteins. However, lipidated polypeptides and integral membrane proteins-an important class of biomolecules-remain enormously challenging to access synthetically owing to poor aqueous solubility of one or more of the fragments under typical ligation conditions. Herein we describe the advent of a reductive diselenide-selenoester ligation (rDSL) method that enables efficient ligation of peptide fragments down to low nanomolar concentrations, without resorting to solubility tags or hybridizing templates. The power of rDSL is highlighted in the efficient synthesis of the FDA-approved therapeutic lipopeptide tesamorelin and palmitylated variants of the transmembrane lipoprotein phospholemman (FXYD1). Lipidation of FXYD1 was shown to critically modulate inhibitory activity against the Na<sup>+</sup>/K<sup>+</sup> pump.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER CHEMICAL SOC
dc.relation.ispartof	Journal of the American Chemical Society
dc.relation.isbasedon	10.1021/jacs.9b12558
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	03 Chemical Sciences
dc.subject.classification	General Chemistry
dc.subject.mesh	Selenium Compounds
dc.subject.mesh	Esters
dc.subject.mesh	Peptides
dc.subject.mesh	Oxidation-Reduction
dc.subject.mesh	Light
dc.subject.mesh	Esters
dc.subject.mesh	Light
dc.subject.mesh	Oxidation-Reduction
dc.subject.mesh	Peptides
dc.subject.mesh	Selenium Compounds
dc.title	Peptide Ligation at High Dilution via Reductive Diselenide-Selenoester Ligation.
dc.type	Journal Article
utslib.citation.volume	142
utslib.location.activity	United States
utslib.for	03 Chemical Sciences
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 Life Sciences
utslib.copyright.status	closed_access	*
dc.date.updated	2021-03-12T03:26:20Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	142
utslib.citation.issue	2

Abstract:

Peptide ligation chemistry has revolutionized protein science by providing access to homogeneously modified peptides and proteins. However, lipidated polypeptides and integral membrane proteins-an important class of biomolecules-remain enormously challenging to access synthetically owing to poor aqueous solubility of one or more of the fragments under typical ligation conditions. Herein we describe the advent of a reductive diselenide-selenoester ligation (rDSL) method that enables efficient ligation of peptide fragments down to low nanomolar concentrations, without resorting to solubility tags or hybridizing templates. The power of rDSL is highlighted in the efficient synthesis of the FDA-approved therapeutic lipopeptide tesamorelin and palmitylated variants of the transmembrane lipoprotein phospholemman (FXYD1). Lipidation of FXYD1 was shown to critically modulate inhibitory activity against the Na⁺/K⁺ pump.

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http://hdl.handle.net/10453/147060