Late-Stage Functionalization of Histidine in Unprotected Peptides.

@article{Noisier2019LateStageFO,
  title={Late-Stage Functionalization of Histidine in Unprotected Peptides.},
  author={Ana{\"i}s F. M. Noisier and Magnus J. Johansson and L. Knerr and M. A. Hayes and W. Drury and E. Valeur and Lara R Malins and R. Gopalakrishnan},
  journal={Angewandte Chemie},
  year={2019}
}
The late-stage functionalization (LSF) of peptides represents a valuable strategy for the design of potent peptide pharmaceuticals by enabling rapid exploration of chemical diversity and offering novel opportunities for peptide conjugation. While the C(sp 2 )-H activation of tryptophan (Trp) is well documented, the resurgence of radical chemistry is opening new avenues for the C-H functionalization of other aromatic side-chains. Herein, we report the first example of LSF at C2 of histidine (His… Expand
13 Citations
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References

SHOWING 1-10 OF 56 REFERENCES
Site-Selective C(sp3)–H Functionalization of Di-, Tri-, and Tetrapeptides at the N-Terminus
TLDR
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 is reported. Expand
Stapled Peptides by Late-Stage C(sp3 )-H Activation.
TLDR
The development of a palladium-catalyzed late-stage C(sp3 )-H activation method for peptide stapling, affording an unprecedented hydrocarbon cross-link is reported. Expand
Bioorthogonal Diversification of Peptides through Selective Ruthenium(II)-Catalyzed C-H Activation.
TLDR
The unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions is illustrated. Expand
Late-Stage Peptide Diversification by Position-Selective C-H Activation.
TLDR
Recent progress in organometallic C-H activation on peptides until June 2018 is summarized, including position- and chemoselective palladium-, ruthenium-, and manganese-catalyzed processes. Expand
Late stage modification of peptides via CH activation reactions
Abstract Recently developed strategies for late stage modification of peptides through C H activation, an arena of contemporary interest in chemical biology and drug discovery, are discussed. ThroughExpand
Late-Stage Peptide Diversification through Cobalt-Catalyzed C-H Activation: Sequential Multicatalysis for Stapled Peptides.
TLDR
An unprecedented cobalt(III)-catalyzed peptide C-H activation is reported, which enables the direct C-h functionalization of structurally complex peptides, and sets the stage for a multicatalytic C- H activation/alkene metathesis/hydrogenation strategy for the assembly of novel cyclic peptides. Expand
New peptide architectures through C–H activation stapling between tryptophan–phenylalanine/tyrosine residues
TLDR
A synthetic strategy for the preparation of unique constrained peptides featuring a covalent bond between tryptophan and phenylalanine or tyrosine residues through an intramolecular palladium-catalysed C–H activation process is described. Expand
Postsynthetic modification of peptides: chemoselective C-arylation of tryptophan residues.
TLDR
The development of new methodologies for the selective and straightforward chemical modification of biomolecules is a scientific challenge that has tremendous implications in drug discovery, as well as in chemical biology and proteomics. Expand
Chemo- and Regioselective Ethynylation of Tryptophan-Containing Peptides and Proteins.
TLDR
It was demonstrated by NMR that the ethynylation occurred selectively at the C2-position of the indole ring of tryptophan, and MS/MS showed that the tryPTophan residues could be modified selectively with Ethynyl functionalities even when the tryptophile was present as a part of the protein. Expand
Peptide modification and cyclization via transition-metal catalysis.
  • Lara R Malins
  • Chemistry, Medicine
  • Current opinion in chemical biology
  • 2018
TLDR
The advances outlined herein facilitate access to high-value peptide targets with promising applications in materials science and drug discovery and markedly extended the scope of conventional peptide modification and bioconjugation strategies. Expand
...
1
2
3
4
5
...