Rapid Formation of Intramolecular Disulfide Bridges using Light: An Efficient Method to Control the Conformation and Function of Bioactive Peptides DOI
Feng He, Yu Chai,

Zizhen Zeng

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(41), С. 22639 - 22648

Опубликована: Окт. 3, 2023

Disulfide bonds are widely found in natural peptides and play a pivotal role stabilizing their secondary structures, which highly associated with biological functions. Herein, we introduce light-mediated strategy to effectively control the formation of disulfides. Our is based on 2-nitroveratryl (oNv), used photolabile motif, serves both as photocaging group an oxidant (after photolysis). We demonstrated that irradiation oNv-caged thiols UV light could release free rapidly oxidized by locally released byproduct nitrosoarene, leading "break-to-bond" fashion. This highlighted situ restoration antimicrobial peptide tachyplesin I (TPI) from its external disulfide-caged analogue TPI-1. TPI-1 exhibits distorted structure diminished function. However, upon irradiation, β-hairpin membrane activity TPI were largely restored via rapid intramolecular disulfide formation. study proposes powerful method regulate conformation function spatiotemporal manner, has significant potential for design disulfide-centered light-responsive systems.

Язык: Английский

Noncanonical Amino Acids in Biocatalysis DOI Creative Commons
Zachary Birch-Price, Florence J. Hardy,

Thomas M. Lister

и другие.

Chemical Reviews, Год журнала: 2024, Номер 124(14), С. 8740 - 8786

Опубликована: Июль 3, 2024

In recent years, powerful genetic code reprogramming methods have emerged that allow new functional components to be embedded into proteins as noncanonical amino acid (ncAA) side chains. this review, we will illustrate how the availability of an expanded set building blocks has opened a wealth opportunities in enzymology and biocatalysis research. Genetic provided insights enzyme mechanisms by allowing introduction spectroscopic probes targeted replacement individual atoms or groups. NcAAs also been used develop engineered biocatalysts with improved activity, selectivity, stability, well enzymes artificial regulatory elements are responsive external stimuli. Perhaps most ambitiously, combination laboratory evolution given rise classes use ncAAs key catalytic elements. With framework for developing ncAA-containing now firmly established, optimistic become progressively more tool armory designers engineers coming years.

Язык: Английский

Процитировано

22
Computational Design, Synthesis, and Photochemistry of Cy7‐PPG, an Efficient NIR‐Activated Photolabile Protecting Group for Therapeutic Applications** DOI Creative Commons
Georgios Alachouzos, Albert M. Schulte, Anirban Mondal

и другие.

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(27)

Опубликована: Фев. 19, 2022

Photolabile Protecting Groups (PPGs) are molecular tools used, for example, in photopharmacology the activation of drugs with light, enabling spatiotemporal control over their potency. Yet, red-shifting PPG wavelengths into NIR range, which penetrates deepest tissue, has often yielded inefficient or insoluble molecules, hindering use PPGs clinic. To solve this problem, we report herein a novel concept design, by transforming clinically-applied NIR-dyes suitable orbital configurations new NIR-PPGs using computational approaches. Using method, demonstrate how Cy7, class dyes possessing ideal properties (NIR-absorption, high absorptivity, excellent aqueous solubility) can be successfully converted Cy7-PPG. We facile synthesis towards Cy7-PPG from accessible precursors and confirm its as most redshifted oxygen-independent NIR-PPG to date (λ

Язык: Английский

Процитировано

40
The fate of the contact ion pair determines the photochemistry of coumarin-based photocleavable protecting groups DOI Creative Commons
Albert M. Schulte, Georgios Alachouzos, Wiktor Szymański

и другие.

Chemical Science, Год журнала: 2024, Номер 15(6), С. 2062 - 2073

Опубликована: Янв. 1, 2024

Improving the efficiency of photocleavable protecting groups is crucial for their application. Here we reveal how fate contact ion pair intermediate plays a key role in defining this efficiency.

Язык: Английский

Процитировано

12
Photochemistry in Medicinal Chemistry and Chemical Biology DOI
Wenyong Zhu, Claire Empel, Sveva Pelliccia

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(6), С. 4322 - 4345

Опубликована: Март 8, 2024

Photochemistry has emerged as a transformative force in organic chemistry, significantly expanding the chemical space accessible for medicinal chemistry. Light-induced reactions enable efficient synthesis of intricate structures and have found applications throughout different stages drug discovery development processes. Moreover, photochemical techniques provide innovative solutions biology, allowing precise spatiotemporal activation targeted delivery. In this Perspective, we highlight already numerous remarkable even more promising future photochemistry chemistry biology.

Язык: Английский

Процитировано

12
BODIPY-based photocages: rational design and their biomedical application DOI
Heng Li, Jun Wang, Lijuan Jiao

и другие.

Chemical Communications, Год журнала: 2024, Номер 60(45), С. 5770 - 5789

Опубликована: Янв. 1, 2024

This highlight reviews various strategies for constructing BODIPY-based photocages, their photodecaging mechanisms, and applications in the biomedical field.

Язык: Английский

Процитировано

8
Applications of Genetic Code Expansion in Studying Protein Post-translational Modification DOI
Jinghao Chen, Yu‐Hsuan Tsai

Journal of Molecular Biology, Год журнала: 2021, Номер 434(8), С. 167424 - 167424

Опубликована: Дек. 28, 2021

Язык: Английский

Процитировано

43
The Construction of Polyphotocage Platform for Anticancer Photochemotherapy DOI
Maomao He, Ran Wang, Ruifeng Zhang

и другие.

Advanced Functional Materials, Год журнала: 2023, Номер 33(26)

Опубликована: Март 22, 2023

Abstract Photocages enable the precise activation of molecular function with light in many research fields, such as anticancer treatment, where remote spatiotemporal control over release an active drug is needed. However, poor physiological stability and tumor accumulation conventional small photocages are significant obstacles to developing efficient therapy vivo. In this study, a new concept “polyphotocage” proposed through photocage–polymer hybrid macromolecular engineering. Photoresponsive Ru complex photocage designed fused PEGylated polycarbonates, resulting polyphotocage. Various drugs can be readily conjugated polyphotocage via coordination linkage, which cut off by red light. The polyphotocages self‐assemble into nanoparticles, enhances demonstrates different‐sized tumorswith high signal‐to‐background ratio. Furthermore, rapid cellular internalization mitochondrial anchoring capability allowed deliver mitochondria, induces dysfunction cell death. These properties ensure effective delivery solid tumors multiple tiny tumors, ultimately inhibiting proliferation. This strategy provides platform for future design drug‐delivery systems cancer photochemotherapy.

Язык: Английский

Процитировано

17
Photocleavable Anionic Glues for Light-Responsive Nanoparticle Aggregates DOI Creative Commons
Jinhua Wang,

Tzuf Shay Peled,

Rafał Klajn

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 4098 - 4108

Опубликована: Фев. 9, 2023

Integrating light-sensitive molecules within nanoparticle (NP) assemblies is an attractive approach to fabricate new photoresponsive nanomaterials. Here, we describe the concept of photocleavable anionic glue (PAG): small trianions capable mediating interactions between (and inducing aggregation of) cationic NPs by means electrostatic interactions. Exposure light converts PAGs into dianionic products incapable maintaining in assembled state, resulting light-triggered disassembly NP aggregates. To demonstrate proof-of-concept, work with organic PAG incorporating UV-cleavable o-nitrobenzyl moiety and inorganic PAG, photosensitive trioxalatocobaltate(III) complex, which absorbs across entire visible spectrum. Both were used prepare either amorphous or regular superlattices a long-range order. These aggregates disassembled rapidly upon exposure for specific time, could be tuned incident wavelength amount used. Selective excitation system combining two results photodecomposition product that deactivates enabling nontrivial profiles under single type external stimulus.

Язык: Английский

Процитировано

16
A photocaged orexin-B for spatiotemporally precise control of orexin signaling DOI Creative Commons
Loïc Duffet,

Petr V. Tatarskiy,

Masaya Harada

и другие.

Cell chemical biology, Год журнала: 2022, Номер 29(12), С. 1729 - 1738.e8

Опубликована: Дек. 1, 2022

Orexin neuropeptides carry out important neuromodulatory functions in the brain, yet tools to precisely control activation of endogenous orexin signaling are lacking. Here, we developed a photocaged orexin-B (photo-OXB) through C-terminal photocaging strategy. We show that photo-OXB is unable activate its cognate receptors dark but releases functionally active native upon uncaging by illumination with UV-visible (UV-vis) light (370–405 nm). established an all-optical assay combining genetically encoded biosensor and used it characterize efficiency spatial profile uncaging. Finally, demonstrated enables optical over fine temporal precision both vitro ex vivo. Thus, our strategy advance chemical biological toolkit introducing method for peptide physiological function.

Язык: Английский

Процитировано

24
Constructing Photoactivatable Protein with Genetically Encoded Photocaged Glutamic Acid DOI Open Access

Xiaochen Yang,

Lei Zhao, Ying Wang

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(40)

Опубликована: Авг. 17, 2023

Genetically replacing an essential residue with the corresponding photocaged analogues via genetic code expansion (GCE) constitutes a useful and unique strategy to directly effectively generate photoactivatable proteins. However, application of this is severely hampered by limited number encoded proteinogenic amino acids. Herein, we report incorporation glutamic acid in E. coli mammalian cells demonstrate their use constructing variants various fluorescent proteins SpyCatcher. We believe genetically Glu would significantly promote design many areas.

Язык: Английский

Процитировано

13