Site-selective C(sp3)-H functionalization of di-, tri-, and tetrapeptides at the N-terminus

Wei Gong, Guofu Zhang, Tao Liu, Ramesh Giri, Jin Quan Yu

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Although the syntheses of novel and diverse peptides rely mainly on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of nonproteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties, such as the thiol group of cysteine or the C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp3)-H bonds of N-terminal amino acids in di-, tri-, and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C-H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp3)-H activation toward postsynthetic modification of a broader range of peptides.

Original languageEnglish (US)
Pages (from-to)16940-16946
Number of pages7
JournalJournal of the American Chemical Society
Volume136
Issue number48
DOIs
StatePublished - Dec 3 2014

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Peptides
Amino acids
Amino Acids
Chemical activation
Sulfhydryl Compounds
Tryptophan
Cysteine
Ligands

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Gong, Wei ; Zhang, Guofu ; Liu, Tao ; Giri, Ramesh ; Yu, Jin Quan. / Site-selective C(sp3)-H functionalization of di-, tri-, and tetrapeptides at the N-terminus. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 48. pp. 16940-16946.
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Site-selective C(sp3)-H functionalization of di-, tri-, and tetrapeptides at the N-terminus. / Gong, Wei; Zhang, Guofu; Liu, Tao; Giri, Ramesh; Yu, Jin Quan.

In: Journal of the American Chemical Society, Vol. 136, No. 48, 03.12.2014, p. 16940-16946.

Research output: Contribution to journalArticle

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AB - Although the syntheses of novel and diverse peptides rely mainly on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of nonproteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties, such as the thiol group of cysteine or the C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp3)-H bonds of N-terminal amino acids in di-, tri-, and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C-H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp3)-H activation toward postsynthetic modification of a broader range of peptides.

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