Macrocyclization strategies for cyclic peptides and peptidomimetics

RSC Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 12(8), P. 1325 - 1351

Published: Jan. 1, 2021

Macrocyclization between head, tail or sidechains is a frequently employed strategy to enhance peptide and peptidomimetic stability, selectivity affinity.

Language: Английский

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Progress and perspectives on directing group-assisted palladium-catalysed C–H functionalisation of amino acids and peptides

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(16), P. 9278 - 9343

Published: Jan. 1, 2021

Peptide modifications can unlock a variety of compounds with structural diversity and abundant biological activity. In nature, peptide modifications, such as functionalisation at the side-chain position amino acids, are performed using post-translational modification enzymes or incorporation unnatural acids. However, accessing these remains challenge for organic chemists. During past decades, selective C-H activation/functionalisation has attracted considerable attention in synthetic chemistry pathway to modification. Various directing group strategies have been discovered that assist activation. particular, bidentate groups enable tuneable reversible coordination now recognised one most efficient methods site-selective activation numerous families compounds. Synthetic chemists harnessed β- γ-positions This method expanded an effective device late stage macrocyclisation total synthesis complex natural products. this review, we discuss various β-, γ-, δ-C(sp3)-H bond reactions acids formation C-X bonds aid their application late-stage

Language: Английский

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Atroposelective synthesis of N-aryl peptoid atropisomers via a palladium(ii)-catalyzed asymmetric C–H alkynylation strategy

Chemical Science, Journal Year: 2021, Volume and Issue: 12(27), P. 9391 - 9397

Published: Jan. 1, 2021

The introduction of chirality into peptoids is an important strategy to determine a discrete and robust secondary structure.

Language: Английский

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Therapeutic stapled peptides: Efficacy and molecular targets

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107137 - 107137

Published: March 23, 2024

Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to original peptides, provides an effective solution accelerate rapid development peptide drugs. Various reviews present stapling chemistries, anchoring residues one- or two-component cyclization, however, therapeutic stapled have not been systematically summarized, especially focusing on various disease-related targets. This review highlights latest advances drug facilitated application technology, including different techniques, synthetic accessibility, applicability biological targets, potential for solving problems, as well current status development. Stapled candidates classified analysed mainly receptor- ligand-based design against diseases, cancer, infectious inflammation, diabetes. is expected provide comprehensive reference rational diseases targets facilitate pharmacokinetic properties.

Language: Английский

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Site-selective modification of peptide backbones

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(23), P. 6720 - 6759

Published: Jan. 1, 2021

Exciting developments in the site-selective modification of peptide backbones are allowing an outstanding fine-tuning conformation, folding ability, and physico-chemical biological properties.

Language: Английский

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Diastereoselective palladium-catalyzed functionalization of prochiral C(sp³)–H bonds of aliphatic and alicyclic compounds

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(16), P. 2612 - 2633

Published: Jan. 1, 2022

Advancements in the palladium-catalyzed functionalization of diastereotopic or prochiral C(sp 3 )–H bonds generating stereogenic centers and stereo-arrays aliphatic compounds have been highlighted.

Language: Английский

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Backbone-enabled modification of peptides with benzoquinone via palladium-catalyzed δ-C(sp²)–H functionalization

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(13), P. 1754 - 1757

Published: Jan. 1, 2024

Backbone-enabled site-selective modification of peptides with benzoquinone via Pd-catalyzed δ-C(sp 2 )–H functionalization has been achieved.

Language: Английский

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Postassembly Modification of Peptides by Histidine-Directed β-C(sp³)–H Arylation of Alanine at the Internal Positions: Overcoming the Inhibitory Effect of Peptide Bonds

Organic Letters, Journal Year: 2024, Volume and Issue: 26(18), P. 3991 - 3996

Published: May 1, 2024

Peptide modification by C(sp3)–H functionalization of residues at the internal positions remains underdeveloped due to inhibitory effect backbone amides. In this study, using histidine (His) as an endogenous directing group, we developed a novel method for β-C(sp3)–H alanine (Ala) diverse peptides. Through approach, wide range linear peptides were modified on side-chain Ala adjacent His afford functionalized in moderate good yield and excellent position selectivity. Furthermore, conjugation with functional molecules such glucuronide, oleanolic acid, dipeptide, fluorophore derivatives was achieved.

Language: Английский

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P^III‐Directed Late‐Stage Ligation and Macrocyclization of Peptides with Olefins by Rhodium Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(31)

Published: May 23, 2022

Transition metal-catalyzed C-H activation is a step-economical strategy for peptide functionalization. Herein, we report the method of late-stage ligation and macrocyclization through rhodium-catalyzed alkylation tryptophan residues at C7 position. This utilizes N-Pt Bu2 directing group tolerates various alkene substrates. Utilizing internal olefins, this study represents first example site-selective deconjugative isomerization. Furthermore, our provides access to macrocycles with unique Trp(C7)-alkyl crosslinks potent cytotoxicity towards cancer cells.

Language: Английский

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Deaminative meta-C–H alkylation by ruthenium(ii) catalysis

Chemical Science, Journal Year: 2021, Volume and Issue: 12(23), P. 8073 - 8078

Published: Jan. 1, 2021

Precise structural modifications of amino acids are importance to tune biological properties or modify therapeutical capabilities relevant drug discovery.

Language: Английский

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