The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans DOI Creative Commons
Yang Liu,

Xinting Zhu,

Kejia Wang

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2021, Номер 8

Опубликована: Ноя. 29, 2021

G-quadruplexes (G4s) are stable non-canonical secondary structures formed by G-rich DNA or RNA sequences. They play various regulatory roles in many biological processes. It is commonly agreed that G4 unwinding helicases key metabolism and function, these processes closely related to physiological pathological In recent years, more functional mechanistic details of have been discovered; therefore, it necessary carefully sort out the current research efforts. Here, we provide a systematic summary from perspective functions molecular mechanisms. First, general introduction about G4s. Next, comprehensively summarize unfolding humans their proposed cellular functions. Then, review study methods Finally, share our on further prospects. We believe this will opportunities for researchers reach frontiers mechanisms human helicases.

Язык: Английский

Expanding the horizons of targeted protein degradation: A non-small molecule perspective DOI Creative Commons
Xiaowei Huang, Fengbo Wu,

Jing Ye

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(6), С. 2402 - 2427

Опубликована: Янв. 21, 2024

Targeted protein degradation (TPD) represented by proteolysis targeting chimeras (PROTACs) marks a significant stride in drug discovery. A plethora of innovative technologies inspired PROTAC have not only revolutionized the landscape TPD but potential to unlock functionalities beyond degradation. Non-small-molecule-based approaches play an irreplaceable role this field. wide variety agents spanning broad chemical spectrum, including peptides, nucleic acids, antibodies, and even vaccines, which prove instrumental overcoming constraints conventional small molecule entities also provided rapidly renewing paradigms. Herein we summarize burgeoning non-small technological platforms PROTACs, three major trajectories, provide insights for design strategies based on novel

Язык: Английский

Процитировано

16
Non-canonical DNA structures: Diversity and disease association DOI Creative Commons

Aparna Bansal,

Shikha Kaushik,

Shrikant Kukreti

и другие.

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Сен. 5, 2022

A complete understanding of DNA double-helical structure discovered by James Watson and Francis Crick in 1953, unveil the importance significance DNA. For last seven decades, this has been a leading light course development modern biology biomedical science. Apart from predominant B-form, experimental shreds evidence have revealed existence sequence-dependent structural diversity, unusual non-canonical structures like hairpin, cruciform, Z-DNA, multistranded such as triplex, G-quadruplex, i-motif forms, etc. The diversity depends on various factors base sequence, ions, superhelical stress, ligands. In response to these factors, polymorphism regulates genes via different processes replication, transcription, translation, recombination. However, altered levels gene expression are associated with many human genetic diseases including neurological disorders cancer. These non-B-DNA expected play key role determining stability, damage repair etc . present review is modest attempt summarize available literature, illustrating occurrence at molecular level environment interaction ligands proteins. This would provide an insight understand biological functions their recognition potential therapeutic targets for diverse diseases.

Язык: Английский

Процитировано

51
Recent Developments in G-Quadruplex Binding Ligands and Specific Beacons on Smart Fluorescent Sensor for Targeting Metal Ions and Biological Analytes DOI
Long Zhao, Farid Ahmed, Yating Zeng

и другие.

ACS Sensors, Год журнала: 2022, Номер 7(10), С. 2833 - 2856

Опубликована: Сен. 16, 2022

The G-quadruplex structure is crucial in several biological processes, including DNA replication, transcription, and genomic maintenance. G-quadruplex-based fluorescent probes have recently gained popularity because of their ease use, low cost, excellent selectivity, sensitivity. This review summarizes the latest applications structures as detectors genome-wide, enantioselective catalysts, disease therapeutics, promising drug targets, smart fluorescence probes. In every section, sensing employing G4 for detection other analytes were introduced, respectively. Since discovery structure, studies been conducted to investigate its conformations, potential, stability, reactivity, selectivity chemical modification, optical properties. formation mechanism advancements detecting different metal ions (Na+, K+, Ag+, Tl+, Cu+/Cu2+, Hg2+, Pb2+) biomolecules (AMP, ATP, DNA/RNA, microRNA, thrombin, T4 PNK, RNase H, ALP, CEA, lipocalin 1, UDG) using sensors based on such dye labels, artificial nucleobase moieties, complexes, intercalating dyes, bioconjugated nanomaterials (AgNCs, GO, QDs, CDs, MOF) described herein. To these extremely efficient responsive agents diagnostic therapeutic medicine, G-quadruplexes also employed a quantitative visualization technique.

Язык: Английский

Процитировано

38
G-Quadruplexes in c-MYC Promoter as Targets for Cancer Therapy DOI Creative Commons

Bárbara Bahls,

Israa M. Aljnadi,

Rita M. Emídio

и другие.

Biomedicines, Год журнала: 2023, Номер 11(3), С. 969 - 969

Опубликована: Март 21, 2023

Cancer is a societal burden demanding innovative approaches. A major problem with the conventional chemotherapeutic agents their strong toxicity and other side effects due to poor selectivity. Uncontrolled proliferation of cancer cells mutations, deletions, or amplifications in genes (oncogenes) encoding for proteins that regulate cell growth division, such as transcription factors, example, c-MYC. The direct targeting c-MYC protein has been attempted but so far unsuccessfully, it lacks definite binding site modulators. Meanwhile, another approach explored since discovery G-quadruplex secondary DNA structures formed guanine-rich sequences promoter region can downregulate this oncogene. Here, we will overview achievements made last decades towards new class anticancer drugs G-quadruplexes cells.

Язык: Английский

Процитировано

29
Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS DOI Creative Commons
Guowei Yin, Jing Huang, Johnny Petela

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 23, 2023

Small GTPases including Ras, Rho, Rab, Arf, and Ran are omnipresent molecular switches in regulating key cellular functions. Their dysregulation is a therapeutic target for tumors, neurodegeneration, cardiomyopathies, infection. However, small have been historically recognized as "undruggable". Targeting KRAS, one of the most frequently mutated oncogenes, has only come into reality last decade due to development breakthrough strategies such fragment-based screening, covalent ligands, macromolecule inhibitors, PROTACs. Two KRASG12C inhibitors obtained accelerated approval treating mutant lung cancer, allele-specific hotspot mutations on G12D/S/R demonstrated viable targets. New methods targeting KRAS quickly evolving, transcription, immunogenic neoepitopes, combinatory with immunotherapy. Nevertheless, vast majority remain elusive, clinical resistance G12C poses new challenges. In this article, we summarize diversified biological functions, shared structural properties, complex regulatory mechanisms their relationships human diseases. Furthermore, review status drug discovery recent strategic progress focused KRAS. The approaches will together promote GTPases.

Язык: Английский

Процитировано

28
Insights on E1-like enzyme ATG7: functional regulation and relationships with aging-related diseases DOI Creative Commons
Jingwei Liu,

Yutong Xiao,

Liangzi Cao

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Март 29, 2024

Autophagy is a dynamic self-renovation biological process that maintains cell homeostasis and responsible for the quality control of proteins, organelles, energy metabolism. The E1-like ubiquitin-activating enzyme autophagy-related gene 7 (ATG7) critical factor initiates classic autophagy reactions by promoting formation extension autophagosome membranes. Recent studies have identified key functions ATG7 in regulating cycle, apoptosis, metabolism associated with occurrence development multiple diseases. This review summarizes how precisely programmed genetic, transcriptional, epigenetic modifications cells relationship between aging-related

Язык: Английский

Процитировано

8
Major Achievements in the Design of Quadruplex-Interactive Small Molecules DOI Creative Commons
Eduarda Mendes, Israa M. Aljnadi,

Bárbara Bahls

и другие.

Pharmaceuticals, Год журнала: 2022, Номер 15(3), С. 300 - 300

Опубликована: Фев. 28, 2022

Organic small molecules that can recognize and bind to G-quadruplex i-Motif nucleic acids have great potential as selective drugs or tools in drug target discovery programs, even the development of nanodevices for medical diagnosis. Hundreds quadruplex-interactive been reported, challenges their design vary with intended application. Herein, we survey major achievements on therapeutic such quadruplex ligands, mode binding, effects upon interaction quadruplexes, consider opportunities exploitation discovery.

Язык: Английский

Процитировано

35
Metal Complexes in Target-Specific Anticancer Therapy: Recent Trends and Challenges DOI Creative Commons
Gemechu Shumi, Tegene Desalegn, Taye B. Demissie

и другие.

Journal of Chemistry, Год журнала: 2022, Номер 2022, С. 1 - 19

Опубликована: Май 17, 2022

Cancer is characterized by abnormal cell differentiation in or on the part of body. The most commonly used chemotherapeutic drugs are developed to target rapidly dividing cells, such as cancer but they also damage healthy epithelial cells. This has serious consequences for normal cells and become responsible development various disorders. Several strategies delivering cytotoxic cancerous sites that limit systemic toxicity other adverse effects have recently been evolved. Among them, biomolecule-conjugated metal complexes-based targeting shown tremendous advantages therapy. review focuses several chemoselective biomolecules-bound complexes prospective therapy-targeted agents. In this review, we presented details extra- intracellular mechanisms We addressed current clinical issues recent therapeutic targeted therapy may pave a way future direction

Язык: Английский

Процитировано

35
Progress of Nanomaterials in Photodynamic Therapy Against Tumor DOI Creative Commons
Lei Chen, Jiahui Huang, Xiaotong Li

и другие.

Frontiers in Bioengineering and Biotechnology, Год журнала: 2022, Номер 10

Опубликована: Май 31, 2022

Photodynamic therapy (PDT) is an advanced therapeutic strategy with light-triggered, minimally invasive, high spatiotemporal selective and low systemic toxicity properties, which has been widely used in the clinical treatment of many solid tumors recent years. Any strategies that improve three elements PDT (light, oxygen, photosensitizers) can efficacy PDT. However, traditional confronted some challenges poor solubility photosensitizers tumor suppressive microenvironment. To overcome related obstacles PDT, various have investigated terms improving (PSs) delivery, penetration excitation light sources, hypoxic In addition, compared a single mode, synergistic multiple modalities such as photothermal therapy, chemotherapy, radiation This review summarizes advances nanomaterials, including metal nanoparticles, liposomes, hydrogels polymers, to enhance efficiency against malignant tumor.

Язык: Английский

Процитировано

29
G-Quadruplexes in Human Telomere: Structures, Properties, and Applications DOI Creative Commons
Yan Xu, Makoto Komiyama

Molecules, Год журнала: 2023, Номер 29(1), С. 174 - 174

Опубликована: Дек. 27, 2023

G-quadruplexes, intricate four-stranded structures composed of G-tetrads formed by four guanine bases, are prevalent in both DNA and RNA. Notably, these play pivotal roles human telomeres, contributing to essential cellular functions. Additionally, the existence DNA:RNA hybrid G-quadruplexes adds a layer complexity their structural diversity. This review provides comprehensive overview recent advancements unraveling intricacies RNA within telomeres. Detailed insights into features presented, encompassing latest developments chemical approaches designed probe G-quadruplex structures. Furthermore, this explores applications targeting Finally, manuscript outlines imminent challenges evolving field, setting stage for future investigations.

Язык: Английский

Процитировано

13