Visible-light-mediated catalyst-free synthesis of unnatural α-amino acids and peptide macrocycles

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 25, 2021

The visible light induced, photocatalysts or photoabsorbing EDA complexes mediated cleavage of pyridinium C-N bond were reported in the past years. Here, we report an ionic compound promote homolytic by exploiting photonic energy from light. This finding is successfully applied deaminative hydroalkylation a series alkenes including naturally occurring dehydroalanine, which provides efficient way to prepare β-alkyl substituted unnatural amino acids under mild and photocatalyst-free conditions. Importantly, using this protocol, cyclization peptide backbone N-terminals realized. Furthermore, use Et3N PPh3 as reductants H2O hydrogen atom source practical advantage. We anticipate that our protocol will be useful synthesis modern drug discovery.

Language: Английский

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Gold(III) Aryl Complexes as Reagents for Constructing Hybrid Peptide-Based Assemblies via Cysteine S-Arylation

Inorganic Chemistry, Journal Year: 2021, Volume and Issue: 60(7), P. 5054 - 5062

Published: March 19, 2021

Organometallic complexes have recently gained attention as competent bioconjugation reagents capable of introducing a diverse array substrates to biomolecule substrates. Here, we detail the synthesis and characterization an aminophosphine-supported Au(III) platform that provides rapid convenient access wide peptide-based assemblies via cysteine S-arylation. This strategy results in formation robust C–S covalent linkages is attractive method for modification complex biomolecules due high functional group tolerance, chemoselectivity, reaction kinetics associated with these arylation reactions. work expands upon existing metal-mediated by class air-stable organometallic serve enabling conjugates higher structural complexity including macrocyclic stapled bicyclic peptides well peptide-functionalized multivalent hybrid nanocluster. organometallic-based approach convenient, one-step peptide functionalization macrocyclization, has potential contribute efforts directed toward developing efficient synthetic strategies building new assemblies.

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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Macrocyclic polymers: Synthesis, purification, properties and applications

Progress in Polymer Science, Journal Year: 2022, Volume and Issue: 134, P. 101606 - 101606

Published: Sept. 6, 2022

Language: Английский

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Construction of Peptide–Isoquinolone Conjugates via Rh(III)-Catalyzed C–H Activation/Annulation

Organic Letters, Journal Year: 2023, Volume and Issue: 25(17), P. 2996 - 3000

Published: April 27, 2023

Herein, we disclose a Rh(III)-catalyzed C–H activation/annulation reaction for the derivatization of Lys-based peptides, in situ affording diverse peptide-isoquinolone conjugates. This approach features racemization-free conditions, high atom- and step-economy, excellent chemo- site-selectivity, broad scope including substrates bearing unprotected Trp Tyr, free Ser Gln, Met residues. The conjugates also display good fluorescent properties with maximum emission wavelengths up to 460 nm. Importantly, preliminary antifungal activity studies indicate that peptide–isoquinolone show potential activities toward crop forest pathogenic fungi, which conjugate Tyr residue exhibits much better B. cinerea Pers. C. chrysosperma than positive control.

Language: Английский

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Unearthing naturally-occurring cyclic antibacterial peptides and their structural optimization strategies

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 73, P. 108371 - 108371

Published: May 3, 2024

Language: Английский

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Chemo-ribosomal synthesis of atropisomeric and macrocyclic peptides with embedded quinolines

Published: June 10, 2024

Expanding the chemical and structural complexity of genetically encoded peptides remains a challenge in peptide therapeutics discovery. Here we report that linear with reactive β- or γ-keto amide at their N-termini can be synthesized ribosomally using vitro translation methods. We show carrying an N-terminal β-keto converted into diverse heterocyclic quinoline-peptide hybrids via Friedländer reactions variety 2-aminoarylcarbonyl co-substrates. Reactions appropriately substituted 2-aminobenzophenones generated stable biaryl atropisomeric axes. In vitro-translated both internal 2-aminoacetophenone motif undergo intramolecular macrocyclization embed quinoline pharmacophore directly within macrocyclic backbone. The introduction ketide building blocks materials post-translational derivatization carbonyl chemistry simultaneously expands diversity provides paradigm for programmed synthesis peptide-derived more closely resemble complex natural products.

Language: Английский

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Unnatural Amino Acids: Strategies, Designs, and Applications in Medicinal Chemistry and Drug Discovery

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(22), P. 19932 - 19965

Published: Nov. 11, 2024

Peptides can operate as therapeutic agents that sit within a privileged space between small molecules and larger biologics. Despite examples of their potential to regulate receptors modulate disease pathways, the development peptides with drug-like properties remains challenge. In quest optimize physicochemical parameters improve target selectivity, unnatural amino acids (UAAs) have emerged critical tools in peptide- peptidomimetic-based drugs. The utility UAAs is illustrated by clinically approved drugs such methyldopa, baclofen, gabapentin addition drug molecules, for example, bortezomib sitagliptin. this Perspective, we outline strategy deployment FDA-approved targets. We further describe modulation using UAAs. Finally, elucidate how these improved pharmacological role played impact progress analogs preclinical stages an emphasis on

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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Metal‐Catalyzed C(sp²)−H Functionalization Processes of Phenylalanine‐ and Tyrosine‐Containing Peptides

European Journal of Inorganic Chemistry, Journal Year: 2021, Volume and Issue: 2021(29), P. 2928 - 2941

Published: June 14, 2021

Abstract The site‐selective chemical diversification of biomolecules constitutes an unmet challenge capital importance within medicinal chemistry and biology. functionalization otherwise unreactive C−H bonds holds great promise for reducing the reliance on existing functional groups, thereby streamlining syntheses. Over last years, a myriad peptide labelling techniques featuring metal‐catalyzed reactions have been developed. Despite wealth reports in field, modification both phenylalanine (Phe) tyrosine (Tyr) compounds upon metal catalysis remain comparatively overlooked. This review highlights these promising tagging strategies, which generally occur through formation challenging 6‐membered metallacycles enable late‐stage peptides tailored fashion.

Language: Английский

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