Hypervalent Iodine Amino Acid Building Blocks for Bioorthogonal Peptide Macrocyclization DOI Creative Commons

Xingyu Liu,

О. V. Мykhailenko, Adriana Faraone

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: May 29, 2024

Abstract Ethynylbenziodoxol(on)es (EB(X)xs) reagents have emerged as useful for peptide/protein modification due to their versatile reactivity and high selectivity. Herein, we report the successful introduction of ethynylbenziodoxoles (EBxs) on different amino acid building blocks (Lys/Orn/Dap), show compatibility with both solid phase peptide synthesis (SPPS) solution (SPS). The selective incorporation EBx core into sequences enable efficient macrocyclizations under mild conditions topologically unique cyclic bicyclic peptides.

Language: Английский

Biocompatible strategies for peptide macrocyclisation DOI Creative Commons
Junming He, Pritha Ghosh, Christoph Nitsche

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(7), P. 2300 - 2322

Published: Jan. 1, 2024

The identification of macrocyclic peptides in drug discovery demands not only advanced screening strategies but also robust and reliable synthetic methodologies to constrain under biocompatible conditions.

Language: Английский

Citations

21
Selective Protein (Post-)modifications through Dynamic Covalent Chemistry: Self-activated SNAr Reactions DOI
Ferran Esteve, J.‐L. Schmitt, Sergii Kolodych

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

SNAr reactions were remarkably accelerated using a pretargeting and activating unit based on dynamic covalent chemistry (DCvC). A Cys attack at the C–F bond aromatic ring of salicylaldehyde derivatives was only observed upon iminium formation with neighboring Lys residue model small peptides. Such self-activation ascribed to stronger electron-withdrawing capability respect that parent aldehyde stabilized transition state reaction, together higher preorganization reactive groups in cationic aldiminium species. This approach further applied for functionalization two antibodies. In both cases, presence group close proximity resulted noteworthy increase bioconjugation yields, excellent chemo-selectivity. Whereas modification an IgG1 antibody led stochastic product distributions, microenvironment selectivity noted when employing IgG4, line lower number residues hinge region latter. Additionally, postfunctionalization modified antibodies attained through exchange tethered derivative hydrazides, representing unprecedented "tag modify" selective strategy DCvC.

Language: Английский

Citations

2
Tryptophan-specific modification and diversification of peptides and proteins DOI
S K Kundu, A. Bandyopadhyay, Rajib Sarkar

et al.

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review provides an account of the tryptophan-specific conjugation peptides and proteins its extensive application in imaging living cells, radiolabelling proteins, protein engineering, etc .

Language: Английский

Citations

2
Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion DOI Creative Commons
Nikolaj G. Koch, Nediljko Budiša

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(16), P. 9580 - 9608

Published: July 2, 2024

Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific archaea. Our Review provides an overview of how once obscure pyrrolysyl-tRNA synthetase (PylRS) tRNA pair, originally responsible for accurately translating enzymes crucial methanogenic metabolic pathways, laid foundation burgeoning field genetic code expansion. primary focus is discussion to successfully engineer PylRS recognize new substrates and exhibit higher

Language: Английский

Citations

14
Cysteine‐Specific Multifaceted Bioconjugation of Peptides and Proteins Using 5‐Substituted 1,2,3‐Triazines DOI Creative Commons
Quan Zuo, Yiping Li,

Xuanliang Lai

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: March 11, 2024

Abstract Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering drug discovery, of which cysteine‐specific modification strategies are prominent inherent nucleophilicity low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives achieve multifaceted bioconjugation targeting cysteine‐containing peptides proteins. On one hand, this represents an inaugural instance employing in biomolecular‐specific within physiological solution. other as powerful combination precision biorthogonality, strategy allows for one‐pot dual‐orthogonal functionalization biomolecules aldehyde group generated simultaneously. 1,2,3‐Triazine with diverse functional groups allow conjugation or proteins, while bi‐triazines enable peptide cyclization dimerization. The examination stability revealed potential reversible modification. This work establishes comprehensive platform identifying cysteine‐selective modifications, providing new avenues peptide‐based development, bioconjugation, chemical biology research.

Language: Английский

Citations

10
Hard and soft electrons and holes DOI Creative Commons
Florian F. Mulks

Chem, Journal Year: 2024, Volume and Issue: 10(9), P. 2724 - 2744

Published: July 8, 2024

The principle of hard and soft acids bases (HSAB) has given chemists a broad understanding the observed selectivity in variety reaction classes. As we become increasingly aware principle's serious limitations, this study provides an alternative approach. distinction between electrons holes (HSEH) adds to our reactivity. Because radicals are typically better stabilized at sites lone pairs sites, can easily distinguish them. Simple electron density differences (from three single-point functional theory [DFT] calculations) be used visualize effect condense into numerical descriptor. usefulness concept is demonstrated by reproducing experimentally reactivity wide range molecules, including larger examples relevant material pharmaceutical sciences.

Language: Английский

Citations

6
Peptide and Protein Cysteine Modification Enabled by Hydrosulfuration of Ynamide DOI Creative Commons
Changliu Wang, Zhenguang Zhao,

Reem Ghadir

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(9), P. 1742 - 1754

Published: Aug. 21, 2024

Efficient functionalization of peptides and proteins has widespread applications in chemical biology drug discovery. However, the chemoselective site-selective modification remains a daunting task. Herein, highly efficient chemo-, regio-, stereoselective hydrosulfuration ynamide was identified as an method for precise by uniquely targeting thiol group cysteine (Cys) residues. This novel could be facilely operated aqueous buffer fully compatible with wide range proteins, including small model large full-length antibodies, without compromising their integrity functions. Importantly, this reaction provides Z-isomer corresponding conjugates exclusively superior stability, offering approach to peptide protein therapeutics. The potential application further exemplified Cys-bioconjugation variety ynamide-bearing functional molecules such molecule drugs, fluorescent/affinity tags, PEG polymers. It also proved redox proteomic analysis through Cys-alkenylation. Overall, study bioorthogonal tool Cys-specific functionalization, which will find broad synthesis peptide/protein conjugates.

Language: Английский

Citations

4
Synthesis and Characterization of Gold(I) N-Heterocyclic Carbenes Complexes Bearing Methacrylate Moiety DOI

Rim Hamdi,

Ida Staccioni,

Julie Gerber

et al.

Journal of Organometallic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 123514 - 123514

Published: Jan. 1, 2025

Language: Английский

Citations

0
Electro-induced C-H/S-H Cross-Coupling for the Functionalization/Macrocyclization of Cysteine-Containing Peptides DOI
Meng Gao,

Fang Xiang,

Jia Deng

et al.

Published: April 7, 2025

Abstract The electrochemical platform that underpins the promising future of selective modifications peptides and proteins, however, is still rather underdeveloped. Here in, an electro-induced umpolung approach enables efficient functionalization/macrocyclization cysteine-containing reported. Notably, this method utilizes simple halogen source takes metal-mediated atom transfer as main pathway to enable in-situ polarity reversal, highlighting unique possibilities associated with activation methods. Under mild conditions, cysteine residue can be well-labelled high chemo-selectivity excellent conversion. This transformation tolerate a wide range valuable enamines, azoles, partners, also utilized macrocyclization tactic for cyclic peptide synthesis other areas.

Language: Английский

Citations

0
Unraveling the nexus: Genomic instability and metabolism in cancer DOI Creative Commons

Vaibhavi Gujar,

Haojian Li, Tanya T. Paull

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115540 - 115540

Published: April 1, 2025

The DNA-damage response (DDR) is a signaling network that enables cells to detect and repair genomic damage. Over the past three decades, inhibiting DDR has proven be an effective cancer therapeutic strategy. Although drugs targeting have received approval for treating various cancers, tumor often develop resistance these therapies, owing their ability undergo energetic metabolic reprogramming. Metabolic intermediates also influence cells' sense oxidative stress, leading impaired redox metabolism, thus creating vulnerabilities. In this review, we summarize recent advances in understanding crosstalk between metabolism. We discuss combination therapies target DDR, vulnerabilities cancer. outline potential obstacles metabolism propose strategies overcome challenges.

Language: Английский

Citations

0