Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes

Henriette N. Tobiesen; Lars A. Leth; Marc V. Iversen; Line Naesborg; Søren Bertelsen; Karl Anker Jørgensen

doi:10.1002/anie.202008513

Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes

Henriette N. Tobiesen, Lars A. Leth, Marc V. Iversen, Line Naesborg, Søren Bertelsen, Karl Anker Jørgensen^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

The first stereoselective, near-equimolar, and metal-free oxidative bioconjugation of amino acids and oligopeptides to aldehydes is presented. Based on a newly developed organocatalytic oxidative concept, the C-terminal and side-chain carboxylic acid functionalities of amino acids and oligopeptides are shown to couple in a stereoselective manner to alpha-branched aldehydes catalyzed by a chiral primary amine and a quinone as oxidizing agent. The oxidative coupling generally proceeds in high yield. For aspartic acid, selective coupling of the side-chain, or the C-terminal carboxylic acid, is demonstrated depending on the protection strategy. The stereoselective, oxidative bioconjugation concept is extended to a series of oligopeptides where coupling to carboxylic acid functionalities is presented. Bioorthogonal linker molecules for further functionalization are obtained by merging the oxidative coupling strategy with the click concept. It is demonstrated that the configuration of the new stereocenter is determined exclusively by the organocatalyst.

Original language	English
Journal	Angewandte Chemie - International Edition
Volume	59
Issue	42
Pages (from-to)	18490-18494
Number of pages	5
ISSN	1433-7851
DOIs	https://doi.org/10.1002/anie.202008513
Publication status	Published - Oct 2020

Keywords

amino acids
bioconjugation
oligopeptides
organocatalysis
stereoselectivity
SELECTIVE BIOCONJUGATION
ALKYLATION
PROTEINS

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10.1002/anie.202008513

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title = "Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes",

abstract = "The first stereoselective, near-equimolar, and metal-free oxidative bioconjugation of amino acids and oligopeptides to aldehydes is presented. Based on a newly developed organocatalytic oxidative concept, the C-terminal and side-chain carboxylic acid functionalities of amino acids and oligopeptides are shown to couple in a stereoselective manner to alpha-branched aldehydes catalyzed by a chiral primary amine and a quinone as oxidizing agent. The oxidative coupling generally proceeds in high yield. For aspartic acid, selective coupling of the side-chain, or the C-terminal carboxylic acid, is demonstrated depending on the protection strategy. The stereoselective, oxidative bioconjugation concept is extended to a series of oligopeptides where coupling to carboxylic acid functionalities is presented. Bioorthogonal linker molecules for further functionalization are obtained by merging the oxidative coupling strategy with the click concept. It is demonstrated that the configuration of the new stereocenter is determined exclusively by the organocatalyst.",

keywords = "amino acids, bioconjugation, oligopeptides, organocatalysis, stereoselectivity, SELECTIVE BIOCONJUGATION, ALKYLATION, PROTEINS",

author = "Tobiesen, {Henriette N.} and Leth, {Lars A.} and Iversen, {Marc V.} and Line Naesborg and S{\o}ren Bertelsen and J{\o}rgensen, {Karl Anker}",

year = "2020",

month = oct,

doi = "10.1002/anie.202008513",

language = "English",

volume = "59",

pages = "18490--18494",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "Wiley - VCH Verlag GmbH & CO. KGaA",

number = "42",

}

Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes. / Tobiesen, Henriette N.; Leth, Lars A.; Iversen, Marc V. et al.
In: Angewandte Chemie - International Edition, Vol. 59, No. 42, 10.2020, p. 18490-18494.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes

AU - Tobiesen, Henriette N.

AU - Leth, Lars A.

AU - Iversen, Marc V.

AU - Naesborg, Line

AU - Bertelsen, Søren

AU - Jørgensen, Karl Anker

PY - 2020/10

Y1 - 2020/10

N2 - The first stereoselective, near-equimolar, and metal-free oxidative bioconjugation of amino acids and oligopeptides to aldehydes is presented. Based on a newly developed organocatalytic oxidative concept, the C-terminal and side-chain carboxylic acid functionalities of amino acids and oligopeptides are shown to couple in a stereoselective manner to alpha-branched aldehydes catalyzed by a chiral primary amine and a quinone as oxidizing agent. The oxidative coupling generally proceeds in high yield. For aspartic acid, selective coupling of the side-chain, or the C-terminal carboxylic acid, is demonstrated depending on the protection strategy. The stereoselective, oxidative bioconjugation concept is extended to a series of oligopeptides where coupling to carboxylic acid functionalities is presented. Bioorthogonal linker molecules for further functionalization are obtained by merging the oxidative coupling strategy with the click concept. It is demonstrated that the configuration of the new stereocenter is determined exclusively by the organocatalyst.

AB - The first stereoselective, near-equimolar, and metal-free oxidative bioconjugation of amino acids and oligopeptides to aldehydes is presented. Based on a newly developed organocatalytic oxidative concept, the C-terminal and side-chain carboxylic acid functionalities of amino acids and oligopeptides are shown to couple in a stereoselective manner to alpha-branched aldehydes catalyzed by a chiral primary amine and a quinone as oxidizing agent. The oxidative coupling generally proceeds in high yield. For aspartic acid, selective coupling of the side-chain, or the C-terminal carboxylic acid, is demonstrated depending on the protection strategy. The stereoselective, oxidative bioconjugation concept is extended to a series of oligopeptides where coupling to carboxylic acid functionalities is presented. Bioorthogonal linker molecules for further functionalization are obtained by merging the oxidative coupling strategy with the click concept. It is demonstrated that the configuration of the new stereocenter is determined exclusively by the organocatalyst.

KW - amino acids

KW - bioconjugation

KW - oligopeptides

KW - organocatalysis

KW - stereoselectivity

KW - SELECTIVE BIOCONJUGATION

KW - ALKYLATION

KW - PROTEINS

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M3 - Journal article

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SN - 1433-7851

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SP - 18490

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JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 42

ER -

Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes

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