Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 2122 - 2131

Published: Jan. 8, 2024

Bioconjugation chemistry has emerged as a powerful tool for the modification of diverse biomolecules under mild conditions. Tetrazole, initially proposed bioorthogonal photoclick handle 1,3-dipolar cyclization with alkenes, was later demonstrated to possess broader photoreactivity carboxylic acids, serving versatile bioconjugation and photoaffinity labeling probe. In this study, we unexpectedly discovered validated between tetrazole primary amine afford new 1,2,4-triazole product. Given significance functionalized N-heterocycles in medicinal chemistry, successfully harnessed serendipitously reaction synthesize both pharmacologically relevant DNA-encoded chemical libraries (DELs) small molecule compounds bearing scaffolds. Furthermore, conditions stable linkage found broad application photoinduced scenarios, spanning from intramolecular peptide macrocyclization templated DNA cross-linking intermolecular proteins. Triazole products on lysine side chains were identified tetrazole-labeled proteins, refining comprehensive understanding photo-cross-linking profiles tetrazole-based probes. Altogether, tetrazole-amine expands current toolbox creates possibilities at interface biology.

Language: Английский

---

Evolution of chemistry and selection technology for DNA-encoded library

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(2), P. 492 - 516

Published: Oct. 11, 2023

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and non-self-replicating phenotypes, generating a diverse world. In analogy with biological world, DEL world can evolve by using central dogma, wherein DNA replicates PCR reactions to amplify genetic codes, sequencing transcripts information, DNA-compatible synthesis translates into phenotypes. Importantly, is key expanding space. Besides, evolution-driven selection system pushes chemicals under selective pressure, i.e., desired strategies. this perspective, we summarized recent advances in synthetic toolbox panning strategies, which will shed light on drug discovery harnessing vitro evolution via DEL.

Language: Английский

---

Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents

Molecules, Journal Year: 2024, Volume and Issue: 29(9), P. 2127 - 2127

Published: May 3, 2024

Neurodegeneration is a gradual decay process leading to the depletion of neurons in both central and peripheral nervous systems, ultimately resulting cognitive dysfunctions deterioration brain functions, alongside decline motor skills behavioral capabilities. Neurodegenerative disorders (NDs) impose substantial socio-economic strain on society, aggravated by advancing age world population absence effective remedies, predicting negative future. In this context, urgency discovering viable therapies critical and, despite significant efforts medicinal chemists developing potential drug candidates exploring various small molecules as therapeutics, regrettably, truly treatment yet be found. Nitrogen heterocyclic compounds, particularly those containing indole nucleus, which has emerged privileged scaffold, have attracted particular attention for variety pharmacological applications. This review analyzes rational design strategy adopted different research groups development anti-neurodegenerative indole-based compounds modulate molecular targets involved NDs, with reference most recent advances between 2018 2023.

Language: Английский

---

Bioinspired Selenium‐Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole‐Scale Medicinal Chemistry and Bioconjugation

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(15)

Published: Feb. 12, 2024

Abstract Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage great importance expanding the toolbox. We report first selenium‐nitrogen exchange (SeNEx) reaction between benzoselenazolones and terminal alkynes (Se−N to Se−C), which inspired by biochemical SeNEx Ebselen cysteine (Cys) residue Se−S). formed selenoalkyne connection readily elaborated, thus endowing this multidimensional diversity. Besides, modular, predictable, high‐yielding, features fast kinetics (k2≥14.43 M −1 s ), excellent group compatibility, works well at miniaturization (nanomole‐scale), opening up many interesting opportunities organo‐Se synthesis bioconjugation, as exemplified sequential (coupled ruthenium‐catalyzed azide‐alkyne cycloaddition (RuAAC) sulfur‐fluoride (SuFEx)), selenomacrocycle synthesis, nanomole‐scale Se‐containing natural product library DNA‐encoded (DEL), late‐stage peptide modification ligation, multiple functionalization proteins. These results indicated that useful developments, established will serve transformative platform in multidisciplinary fields such synthetic chemistry, material science, chemical biology, medical drug

Language: Английский

---

Organoselenium compounds in medicinal chemistry

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(17)

Published: May 23, 2024

Abstract The chemical and biological interest in this element the molecules bearing selenium has been exponentially growing over years. Selenium, formerly designated as a toxin, becomes vital trace for life that appears selenocysteine its dimeric form, selenocystine, active sites of selenoproteins, which catalyze wide variety reactions, including detoxification reactive oxygen species modulation redox activities. From point view drug developments, organoselenium drugs are isosteres sulfur‐containing oxygen‐containing with advantage presence atom confers antioxidant properties high lipophilicity, would increase cell membrane permeation leading to better oral bioavailability. This statement is paramount relevance considering big number clinically employed compounds sulfur or atoms their structures nucleosides carbohydrates. Thus, article we have focused on relevant features application medicinal chemistry. With increasing chemistry, attempted highlight most significant published data subject, mainly concentrating analysis last In consequence, recent advances pharmacological discussed.

Language: Английский

---

Using DNA-encoded libraries of fragments for hit discovery of challenging therapeutic targets

Expert Opinion on Drug Discovery, Journal Year: 2024, Volume and Issue: 19(6), P. 725 - 740

Published: May 16, 2024

Introduction The effectiveness of Fragment-based drug design (FBDD) for targeting challenging therapeutic targets has been hindered by two factors: the small library size and complexity fragment-to-hit optimization process. DNA-encoded (DEL) technology offers a compelling robust high-throughput selection approach to potentially address these limitations.

Language: Английский

---

FeCl3-Catalyzed Oxidative Diselenylation of Pyrrole-tethered Indoles

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

Published: Jan. 1, 2025

A mild and efficient FeCl 3 -catalyzed oxidative diselenylation of pyrrole-tethered indoles has been achieved by using RSeSeR as the source selenium m -chloroperoxybenzoic acid ( CPBA) oxidant (yields 17–70%).

Language: Английский

---

Optimized ebselen derivatives as novel potent Escherichia coli β-glucuronidase covalent allosteric inhibitors

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117571 - 117571

Published: March 1, 2025

Language: Английский

---

Strategic application of CuAAC click chemistry in the modification of natural products for anticancer activity

European Journal of Medicinal Chemistry Reports, Journal Year: 2023, Volume and Issue: 9, P. 100113 - 100113

Published: Sept. 7, 2023

Natural products play a key role in the history of human drug discovery, and especially for anticancer agents. Copper(I)-catalyzed alkyne-azide [3+2] cycloaddition (CuAAC) reaction is perhaps most powerful method efficient modification complex natural products, enabling direct incorporation various functional groups accompanied by formation multifunctional 1,2,3-triazole motif, which could not only serve as an basic hydrophilic connecting group but also bioisosteres 5- or 6-membered heterocycles amide group, thus facilitating improvement activities and/or drug-like properties. This contribution extensively summarizes state-of-the-art application activity. The aim to gain deep understanding fruitful achievements well limitations CuAAC click chemistry product activity, provide perspectives directions regarding future studies medicinal chemistry.

Language: Английский

---

Calcium(II)-Mediated Three-Component Selenofunctionalization of Alkenes under Mild Conditions

Organic Letters, Journal Year: 2023, Volume and Issue: 25(45), P. 8095 - 8099

Published: Nov. 8, 2023

A mild and general protocol involving amnio- oxyselenation of diverse alkenes for the efficient synthesis organo-Se compounds is achieved via an environmentally benign calcium-catalyzed three-component reaction. This selenofunctionalization reaction exhibits excellent substrate/functional group tolerance high levels chemo- regioselectivity. Its utility was exemplified in late-stage functionalization even aggregation-induced emission luminogen labeling compounds.

Language: Английский

---