ERAP1 activity modulates the immunopeptidome but also affects the proteome, metabolism and stress responses in cancer cells DOI Creative Commons
Martha Nikopaschou, Martina Samiotaki,

Elli-Anna Stylianaki

et al.

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100964 - 100964

Published: April 1, 2025

Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) metabolizes peptides inside the ER and shapes peptide repertoire available for binding to Major Histocompatibility Complex Class I molecules (MHC-I). However, it may have additional effects on cellular homeostasis, which not been explored. To address these questions, we used both genetic silencing of ERAP1 expression as well treatment with a selective allosteric inhibitor probe changes in immunopeptidome proteome A375 melanoma cancer cell line. We observed significant shifts methods functional disruption, were distinct each method. Both inhibition led an enhancement, albeit slight, tumor killing by stimulated human PBMCs proteomic alterations pathways related metabolism stress. Similar also leukemia line THP-1. Biochemical analyses suggested that affected sensitivity stress, reactive oxygen species production mitochondrial metabolism. Although proteomics significant, their potential shaping was limited since only 9.6% differentially presented belonged proteins altered 4.0% represented shifts. Taken together, our findings suggest modulation activity can generate unique immunopeptidomes, mainly due processing ER, but induce metabolic state further cells.

Language: Английский

Metallodrugs are unique: opportunities and challenges of discovery and development DOI Creative Commons
Elizabeth J. Anthony, Elizabeth M. Bolitho, Hannah E. Bridgewater

et al.

Chemical Science, Journal Year: 2020, Volume and Issue: 11(48), P. 12888 - 12917

Published: Jan. 1, 2020

The vital roles of metals in nutrients and medicines are not accessible to purely organic compounds.

Language: Английский

Citations

535
Nanocatalytic Medicine DOI
Bowen Yang, Yu Chen, Jianlin Shi

et al.

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(39)

Published: July 22, 2019

Abstract Catalysis and medicine are often considered as two independent research fields with their own respective scientific phenomena. Promoted by recent advances in nanochemistry, large numbers of nanocatalysts, such nanozymes, photocatalysts, electrocatalysts, have been applied vivo to initiate catalytic reactions modulate biological microenvironments for generating therapeutic effects. The rapid growth biomedical applications nanocatalysts has led the concept “nanocatalytic medicine,” which is expected promote further advance a subdiscipline nanomedicine. high efficiency selectivity catalysis that chemists strived achieve past century can be ingeniously translated into efficacy mitigated side effects theranostics using medicine” steer optimized outcomes. Here, rationale behind construction nanocatalytic eludicated based on essential reaction factors (catalysts, energy input, reactant). Recent this burgeoning field then comprehensively presented mechanisms nanosystems conferred theranostic functions discussed detail. It believed an emerging modality will play more important role

Language: Английский

Citations

519
Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features DOI Creative Commons
Yanguang Cong,

Sijin Yang,

Xiancai Rao

et al.

Journal of Advanced Research, Journal Year: 2019, Volume and Issue: 21, P. 169 - 176

Published: Oct. 12, 2019

The infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is a global threat to public health. Vancomycin remains one of the first-line drugs for treatment MRSA infections. However, S. isolates with complete resistance vancomycin have emerged in recent years. Vancomycin-resistant (VRSA) mediated vanA gene cluster, which transferred from vancomycin-resistant enterococcus. Since first VRSA isolate was recovered Michigan, USA 2002, 52 strains been isolated worldwide. In this paper, we review latest progresses VRSA, highlighting its mechanism, characteristics infections, as well clinical treatments.

Language: Английский

Citations

415
Cuproptosis: Harnessing Transition Metal for Cancer Therapy DOI
Wuyin Wang, Wentao Mo, Zishan Hang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Language: Английский

Citations

90
A Review of the Current State of Magnetic Force Microscopy to Unravel the Magnetic Properties of Nanomaterials Applied in Biological Systems and Future Directions for Quantum Technologies DOI Creative Commons
Robert Winkler,

M. Ciria,

Margaret Ahmad

et al.

Nanomaterials, Journal Year: 2023, Volume and Issue: 13(18), P. 2585 - 2585

Published: Sept. 18, 2023

Magnetism plays a pivotal role in many biological systems. However, the intensity of magnetic forces exerted between bodies is usually low, which demands development ultra-sensitivity tools for proper sensing. In this framework, force microscopy (MFM) offers excellent lateral resolution and possibility conducting single-molecule studies like other single-probe (SPM) techniques. This comprehensive review attempts to describe paramount importance applications by highlighting MFM's main advantages but also intrinsic limitations. While working principles are described depth, article focuses on novel micro- nanofabrication procedures MFM tips, enhance response signal tested biomaterials compared commercial nanoprobes. work depicts some relevant examples where can quantitatively assess performance nanomaterials involved systems, including magnetotactic bacteria, cryptochrome flavoproteins, nanoparticles that interact with animal tissues. Additionally, most promising perspectives field highlighted make reader aware upcoming challenges when aiming toward quantum technologies.

Language: Английский

Citations

61
Atomic-level design of metalloenzyme-like active pockets in metal–organic frameworks for bioinspired catalysis DOI
Weiqing Xu, Yu Wu, Wenling Gu

et al.

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 53(1), P. 137 - 162

Published: Nov. 29, 2023

Natural metalloenzymes with astonishing reaction activity and specificity underpin essential life transformations. Nevertheless, enzymes only operate under mild conditions to keep sophisticated structures active, limiting their potential applications. Artificial that recapitulate the catalytic of can not circumvent enzymatic fragility but also bring versatile functions into practice. Among them, metal-organic frameworks (MOFs) featuring diverse site-isolated metal sites supramolecular have emerged as promising candidates for move toward unparalleled properties behaviour enzymes. In this review, we systematically summarize significant advances in MOF-based metalloenzyme mimics a special emphasis on active pocket engineering at atomic level, including primary secondary coordination spheres. Then, deep understanding mechanisms advanced applications are discussed. Finally, perspective emerging frontier research is provided advance bioinspired catalysis.

Language: Английский

Citations

61
Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery DOI Creative Commons
Christine N. Morrison, Kathleen E. Prosser, Ryjul W. Stokes

et al.

Chemical Science, Journal Year: 2019, Volume and Issue: 11(5), P. 1216 - 1225

Published: Dec. 12, 2019

Fragment-based drug discovery (FBDD) using 3-dimensional metallofragments is a new strategy for the identification of bioactive molecules.

Language: Английский

Citations

119
Emerging Opportunities To Manipulate Metal Trafficking for Therapeutic Benefit DOI Open Access
Elizabeth W. Hunsaker, Katherine J. Franz

Inorganic Chemistry, Journal Year: 2019, Volume and Issue: 58(20), P. 13528 - 13545

Published: June 19, 2019

The indispensable requirement for metals in life processes has led to the evolution of sophisticated mechanisms that allow organisms maintain dynamic equilibria these ions. This control level, speciation, and availability a variety metal ions allows sustain biological while avoiding toxicity. When functioning properly, cells return their homeostatic set points following shifts or other stressors. These periods transition, when are state flux which they work regain homeostasis, present windows opportunity pharmacologically manipulate targets associated with metal-trafficking pathways ways could either facilitate homeostasis recovery cellular function further push outside into distress. purpose this Viewpoint is highlight emerging opportunities chemists chemical biologists develop compounds therapeutic benefit.

Language: Английский

Citations

91
Pharmacokinetics and Drug–Drug Interactions of Long-Acting Intramuscular Cabotegravir and Rilpivirine DOI Creative Commons
Daryl Hodge, David Back,

Sara Gibbons

et al.

Clinical Pharmacokinetics, Journal Year: 2021, Volume and Issue: 60(7), P. 835 - 853

Published: April 8, 2021

Combined antiretroviral treatments have significantly improved the morbidity and mortality related to HIV infection, thus transforming infection into a chronic disease; however, efficacy of is highly dependent on ability infected individuals adhere life-long drug combination therapies. A major milestone in treatment marketing long-acting intramuscular drugs cabotegravir rilpivirine, allowing for infrequent administration, with potential improve adherence therapy satisfaction. Intramuscular administration rilpivirine leads differences pharmacokinetics drug-drug interaction (DDI) profiles compared oral administration. notable difference long elimination half-life which reaches 5.6-11.5 weeks 13-28 41 45 h, respectively, their Cabotegravir low cause DDIs, however these can be victims DDIs. mainly metabolized by UGT1A1, CYP3A4, therefore agents are susceptible DDIs inhibitors, particularly inducers drug-metabolizing enzymes. has advantage eliminating occurring at gastrointestinal level, interactions still occur hepatic level. This review provides insight summarizes pharmacology rilpivirine. Particular emphasis placed DDI after drugs.

Language: Английский

Citations

91
Tropolone natural products DOI
Huijuan Guo, Dávid Roman, Christine Beemelmanns

et al.

Natural Product Reports, Journal Year: 2018, Volume and Issue: 36(8), P. 1137 - 1155

Published: Dec. 17, 2018

Covering: 2008 to 2018 This review provides a comprehensive overview of newly discovered natural products containing tropolonoid motif covering up and depicts the ecological context in which they have been isolated. has strong focus on describing different analytical tools molecular biological approaches used identify underlying biosynthetic pathways.

Language: Английский

Citations

86