Russian Journal of Bioorganic Chemistry最新文献

{"title":"Research Progress on Small-Molecule Inhibitors Targeting Salt-Induced Kinases","authors":"Shuai Li,&nbsp;Wen-ting Xia","doi":"10.1134/S1068162025603647","DOIUrl":"10.1134/S1068162025603647","url":null,"abstract":"<p>As prominent members of the AMPK family, salt-induced kinases (SIKs) play pivotal roles in regulating cellular metabolism, immune responses, and the tumor microenvironment. Aberrant SIK expression is closely linked to oncogenesis, metabolic disorders, and inflammatory diseases. Consequently, small-molecule inhibitors targeting SIKs have emerged as a major research focus. By blocking SIK kinase activity to modulate downstream signaling pathways—such as the CRTC/CREB and LKB1/AMPK axes—these inhibitors exhibit potent antitumor and immunomodulatory activities. The FDA-approved multi-kinase inhibitors dasatinib and bosutinib strongly inhibit SIKs at low nanomolar concentrations (IC₅₀ &lt; 10 nM); originally developed for leukemia, they have demonstrated robust anti-inflammatory and immunomodulatory efficacy in preclinical models. Furthermore, several newly developed SIK inhibitors display high selectivity and nanomolar potency. This review systematically analyzes and summarizes the structural characteristics and physiological activities of diverse SIK inhibitors reported to date. Additionally, we propose a structural reclassification of these novel inhibitors, evaluating their therapeutic efficacy across various malignancies and discussing their clinical potential. This comprehensive overview aims to accelerate the clinical translation of highly selective SIK inhibitors, offering new avenues for multidimensional interventions in tumor progression.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Current State of the Antimicrobial Resistance Problem in Russia: Risks and Responses","authors":"O. V. Kisil,&nbsp;V. S. Sadykova,&nbsp;A. E. Shchekotikhin","doi":"10.1134/S1068162026602478","DOIUrl":"10.1134/S1068162026602478","url":null,"abstract":"<p>Antibiotics are the most important antimicrobial agents that have become the main means in humanity's fight today against infectious diseases. However, their widespread and often unjustified use has led to the development in infectious pathogens of antimicrobial resistance (AMR). The phenomenon of AMR is the ability of microorganisms (including bacteria, microscopic fungi, and parasites) to survive and continue to grow under conditions of exposure to medications designed to inhibit them. Infections caused by AMR microorganisms are not only difficult to treat but are also associated with an increased risk of severe disease and even death. This review analyzes research articles on the problem of antimicrobial resistance published in open electronic databases over the past 5 years, as well as materials from the WHO and international surveillance systems for antimicrobial resistance. The results obtained can be used to formulate recommendations for improving the effectiveness of development and use of antimicrobial agents.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Antibacterial Activity of 3′- and 5′-Alkylamino Derivatives of Thymidine, Uridine, and 5-Methyluridine","authors":"D. A. Makarov,&nbsp;M. V. Jasko,&nbsp;I. L. Karpenko,&nbsp;D.V. Yanvarev,&nbsp;E. V. Urbina,&nbsp;B. F. Vasilyeva,&nbsp;O. V. Efremenkova,&nbsp;M.V. Demiankova,&nbsp;S. N. Kochetkov,&nbsp;L. A. Alexandrova","doi":"10.1134/S1068162026602557","DOIUrl":"10.1134/S1068162026602557","url":null,"abstract":"<p><b>Objective:</b> This study aims to design, synthesize, and evaluate a novel series of pyrimidine nucleoside derivatives modified with long-chain 3′- and 5′-alkylamino substituents as a strategy to overcome evolving bacterial resistance by targeting unconventional pathways in Gram-positive pathogens. <b>Methods:</b> Novel 3′- and 5′-modified thymidine, uridine, and 5-methyluridine analogs were synthesized via site-specific tosylation, nucleophilic substitution with azide or fatty amines, and subsequent reductive amination. The chemical structures of all synthesized compounds were verified using UV, ¹H, and ¹³C NMR spectroscopy, and high-resolution mass spectrometry (HRMS). <i>In vitro</i> cytotoxicity was assessed against the A549 cell line using the standard MTT assay, while antibacterial efficacy was determined via minimum inhibitory concentration (MIC) evaluations against a panel of six Gram-positive bacterial strains, including <i>Staphylococcus aureus</i> (MRSA/MSSA) and <i>Mycobacterium smegmatis</i>. <b>Results and Discussion:</b> Target derivatives <b>IIIa–IIIb</b>, <b>VII</b>, <b>IXa–IXc</b>, and <b>XI</b> exhibited moderate cytotoxicity with CD₅₀ values ranging from 20 to 50 µM. In antibacterial screenings, the ribothymidine and thymidine derivatives <b>VII</b>, <b>IXc</b>, and <b>XI</b>, bearing an extended C₁₃ aminotridecyl chain, demonstrated exceptional potency. Their inhibitory profiles were comparable to clinically established reference antibiotics and significantly outperformed previously reported <i>N</i>⁴-alkylnucleosides. Conversely, shortening the alkyl chain component (<b>IXa</b>) completely abolished antibacterial efficacy, highlighting a stringent structure–activity relationship (SAR) governed by lipophilic chain length. <b>Conclusions:</b> We have successfully established efficient synthetic routes to access novel lipidated pyrimidine nucleosides. The identification of highly potent aminotridecyl-functionalized thymidine derivatives provides a promising molecular platform for the further development of specialized small-molecule counter-measures against multidrug-resistant Gram-positive infections.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Pharmacological Evaluation, Molecular Docking, and In Silico ADMET Profiling of Novel Ibuprofen–Chalcone Hybrids as Potent Anti-Inflammatory Agents","authors":"Bijal Nilesh Patel,&nbsp;Rati Kailash Prasad Tripathi","doi":"10.1134/S1068162025603337","DOIUrl":"10.1134/S1068162025603337","url":null,"abstract":"<p><b>Objective:</b> Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are severely limited by systemic toxicities. To address these constraints, we designed and synthesized a novel series of ibuprofen–chalcone hybrid molecules, capitalizing on a molecular hybridization strategy to merge the core therapeutic pharmacophore of ibuprofen with the versatile, highly biocompatible scaffolds of chalcone derivatives. <b>Methods:</b> We comprehensively characterized the synthesized hybrids using robust spectroscopic techniques. Their biological efficacy was validated via systematic <i>in vitro</i> assays evaluating cyclooxygenase (COX-1/COX-2) inhibition and antioxidant capacities, followed by rigorous <i>in vivo</i> models of anti-inflammatory kinetics, analgesic potencies, and acute ulcerogenic safety profiles. Complementary mechanistic insights were obtained through <i>in silico</i> molecular docking experiments and predictive ADMET profiling. <b>Results and Discussion:</b> Our screening identified compound 6c as the lead candidate, exhibiting highly potent dual COX inhibition (COX-1 IC₅₀ = 1.77 ± 0.01 μM; COX-2 IC₅₀ = 9.17 ± 0.04 μM). Calculation of the selectivity index (SI = COX-2 IC₅₀/COX-1 IC₅₀ = 5.18) confirmed a pronounced preferential affinity for the COX-1 isoform. Crucially, <i>in vivo</i> functional assays demonstrated that compound 6c elicits superior anti-inflammatory and analgesic activities compared to parent ibuprofen, while concomitantly abrogating classic NSAID-induced gastric irritation. Radical scavenging metrics confirmed robust antioxidant functionality across the hybrid series. Molecular docking trajectories corroborated these phenotypic outcomes, revealing highly favorable structural binding conformations and optimal interaction energies within the catalytic pockets of both COX isoforms. Furthermore, predictive <i>in silico</i> ADMET simulations forecasted excellent drug-like characteristics, high oral bioavailability, and a favorable safety margin with minimal systemic toxicity indices for the lead hybrids. <b>Conclusions:</b> Taken together, our findings demonstrate that these novel ibuprofen–chalcone hybrids represent a highly promising therapeutic class of anti-inflammatory leads capable of circumventing the pathological side effects that typically hamper traditional NSAID regimens. These results strongly warrant subsequent preclinical validation and expanded structure–activity relationship (SAR) optimizations.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dyslipidaemia: Pathophysiology, Epidemiology, Diagnostic Advances, and Emerging Therapeutic Strategies","authors":"Amjad Mahmood Qadir,&nbsp;Rebaz Anwar Omer,&nbsp;Hemn A. H. Barzani,&nbsp;Seerwan Hamadameen Sulaiman","doi":"10.1134/S1068162025603581","DOIUrl":"10.1134/S1068162025603581","url":null,"abstract":"<p>Dyslipidaemia, characterized by aberrant circulating lipid and lipoprotein profiles, remains a primary driver of atherogenesis and cardiovascular disease (CVD), underlying substantial global morbidity and mortality. This review elucidates the complex pathophysiology, epidemiological dynamics, and genetic architectures defining dyslipidaemia, delineating primary hereditary molecular defects from secondary acquired etiologies. We highlight recent paradigms in molecular biology, advanced lipid biomarkers surpassing conventional lipid panels, and innovative imaging modalities that have collectively refined cardiovascular risk stratification and diagnostic precision. Furthermore, this work addresses the socioeconomic determinants and lifestyle factors that modulate prevalence and confound clinical management. Current therapeutic regimens—ranging from behavioral modifications and established pharmacological agents (statins, ezetimibe, and PCSK9 inhibitors) to emerging RNA-targeted therapeutics—are critically evaluated. We discuss persistent barriers to patient adherence and the transformative potential of precision medicine, driven by clinical genomics and targeted molecular interventions. Finally, we outline prospective paradigms integrating multi-omics frameworks, novel diagnostics, and psychosocial variables to mitigate the global burden of dyslipidaemia-mediated cardiovascular pathologies.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Benzimidazole–Isatin Hybrids as Potential Therapeutics for Alzheimer’s Disease: Design, Microwave-Assisted Synthesis, and Structure–Activity Relationship","authors":"Fatih Yılmaz,&nbsp;Gülay Akyüz","doi":"10.1134/S1068162025604355","DOIUrl":"10.1134/S1068162025604355","url":null,"abstract":"<p><b>Objective:</b> A novel series of benzimidazole–isatin hybrid compounds was designed and synthesized to evaluate their inhibitory activity against acetylcholinesterase (AChE) and establish comprehensive structure–activity relationships (SAR). <b>Methods:</b> Target hybrids and intermediate precursors were synthesized using both conventional heating and microwave-assisted protocols. Structural elucidation of all synthesized compounds was unequivocally performed using ¹H, ¹³C NMR, high-resolution mass spectrometry (HRMS), and elemental analysis. <b>Results and Discussion:</b> Biological evaluation revealed that integration of the isatin scaffold significantly enhanced AChE inhibitory potency compared with that of the isatin-free intermediate precursors. Notably, several hybrid derivatives displayed superior inhibitory activity relative to the reference drug galantamine (IC₅₀ = 56.4 ± 0.7 µM). SAR analysis demonstrated that electron-withdrawing substituents on the benzyl moiety, in synergy with halogenation on the isatin ring, substantially boosted AChE inhibition. <b>Conclusions:</b> This study underscores microwave irradiation as a highly efficient and superior synthetic approach, establishing benzimidazole–isatin hybrids—most notably compound <b>Vi</b>—as promising pharmacophoric scaffolds for drug development targeting Alzheimer’s disease.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomaterials in Optical Biosensors for Nucleic Acid Detection","authors":"A. M. Isakova,&nbsp;O. Y. Pokatova,&nbsp;M. S. Rubel","doi":"10.1134/S1068162026603277","DOIUrl":"10.1134/S1068162026603277","url":null,"abstract":"<p>This review presents a comprehensive overview of modern nanomaterial-based biosensors for nucleic acid detection, with a particular focus on optical, colorimetric, and surface-enhanced Raman spectroscopy (SERS) methods that operate without enzymes or external labels. The fundamental principle underlying many of these platforms is the specific hybridization between a probe and a complementary target nucleic acid sequence, which triggers a measurable optical signal change. Noble metal nanoparticles (gold and silver), quantum dots, upconversion nanoparticles (UCNPs), graphene oxide, and various nanoclusters serve as the core signal transducers, exploiting phenomena such as fluorescence resonance energy transfer (FRET), localized surface plasmon resonance (LSPR), and nanozyme activity. Fluorescence-based sensors rely on the quenching and restoration of emission from fluorophores (e.g., quantum dots, UCNPs, silver nanoclusters) in the presence of graphene oxide or gold nanoparticles as acceptors, with detection limits reaching femtomolar concentrations. Colorimetric methods offer the distinct advantage of visual readout without instrumentation, leveraging the distance-dependent aggregation of gold or silver nanoparticles, which produces a visible color shift from red to blue or yellow to red upon target hybridization. SERS-based approaches provide ultra-sensitive molecular fingerprinting through electromagnetic field enhancement on plasmonic metal surfaces, enabling direct detection of DNA or RNA via intrinsic nucleobase vibrations. SPR directly detects changes in the refractive index occurring at the sensor surface and is capable of real-time monitoring. This makes it possible not only to confirm the binding but also to observe the kinetics of the process. These biosensors have been successfully applied to detect clinically and environmentally significant pathogens including SARS-CoV-2, HIV, MERS-CoV, <i>Mycobacterium tuberculosis</i>, etc—as well as cancer-associated biomarkers. The feasibility of point-of-care analysis has been demonstrated using paper-based platforms, validation in artificial and real saliva and whole serum, highlighting the practical potential of these technologies.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational Design and Screening of Inhibitors Using Recombinant Metallo-β-Lactamases","authors":"A. S. Tikhomirov,&nbsp;V. G. Grigorenko,&nbsp;G. V. Presnova,&nbsp;M. Yu. Rubtsova,&nbsp;T. S. Shkuratova,&nbsp;P. Tiuleanu,&nbsp;A. M. Egorov,&nbsp;A. E. Shchekotikhin","doi":"10.1134/S1068162026602818","DOIUrl":"10.1134/S1068162026602818","url":null,"abstract":"<p><b>Objective:</b> A comparative study of the affinity and inhibitory activity of derivatives of three groups of heterocyclic carboxylic acids against metallo-β-lactamases (MBLs) of the NDM and VIM families was performed. <b>Methods:</b> The study utilized recombinant enzymes, differential scanning fluorimetry, and enzyme kinetics. <b>Results and Discussion:</b> The structure of the heterocyclic ring, the nature of the substituents, and the presence of a carboxyl group were shown to significantly influence both the inhibition efficiency and the spectrum of inhibitory activity of the compounds against different types of MBLs. Dipicolinic acid derivatives were found to exhibit activity primarily against NDM-1, acting via a chelating mechanism based on the stripping of zinc ions from the active site of the enzyme. In contrast, inhibition of MBLs by indole-2- and pyrrole-2-carboxylic acid derivatives is not associated with nonspecific chelation of metal ions. Indole-2-carboxylic acid derivatives, which are capable of effectively inhibiting both NDM-1 and VIM-2, hold the greatest promise for further research toward the development of a universal pan-inhibitor of clinically significant MBLs. At the same time, structural optimization of their pyrrole analogues yielded compounds that inhibit NDM-1 with IC₅₀ values in the nanomolar range, confirming the high potential of this scaffold for the development of selective NDM inhibitors. <b>Conclusions:</b> These results advance our understanding of the structure–activity relationships among MBL inhibitors and form the basis for the further rational design and optimization of lead compounds.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-Delivery Systems of Antibiotics for Combating Resistant Forms of Tuberculosis","authors":"I. M. Le-Deygen,&nbsp;I. M. Kolmogorov,&nbsp;A. A. Skuredina,&nbsp;N. L. Klyachko,&nbsp;I. A. Vasilyeva,&nbsp;A. G. Samoilova,&nbsp;V. V. Avdeev,&nbsp;A. I. Gaida,&nbsp;T. E. Tyulkova","doi":"10.1134/S1068162026602466","DOIUrl":"10.1134/S1068162026602466","url":null,"abstract":"<p>Current approaches to the development of co-delivery systems for two or more active agents for the therapy of tuberculosis are systematized. The physicochemical properties of key anti-tuberculosis drugs (bedaquiline, pretomanid, linezolid, moxifloxacin, delamanid, clofazimine) that determine the choice of carrier are reviewed. The main types of nanocarriers for co-delivery are analyzed: functionalized liposomes, polymeric nanoparticles, metal-organic frameworks, and hybrid systems with spatial separation of drugs. Mechanisms for combating resistant forms of tuberculosis using co-delivery are discussed, including synergistic action, modulation of the infection microenvironment, and optimization of pharmacokinetics. Particular attention is paid to combinations of antibiotics with antimicrobial peptides, adjuvants (flavonoids, essential oils, vitamins, efflux pump inhibitors), and unconventional agents (nitric oxide donors, fluoxetine, bacteriophage enzymes). It is shown that co-delivery systems provide synergistic action, multiple reduction of minimum inhibitory concentration, prolonged release, and the possibility of reducing dosing frequency to once weekly. Key barriers to clinical translation (scalability, standardization, toxicity, regulatory challenges) are identified, and promising frontiers are outlined: smart systems responsive to the microenvironment, use of artificial intelligence for predicting optimal combinations, fully biodegradable MOFs, and co-delivery of three or more agents with different mechanisms of action.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosensors for Detecting Trinucleotide Repeat Expansions","authors":"P. S. Luganskaya,&nbsp;E. S. Perepelitsa,&nbsp;A. A. Rubel,&nbsp;M. S. Rubel","doi":"10.1134/S1068162026603514","DOIUrl":"10.1134/S1068162026603514","url":null,"abstract":"<p>Short tandem repeat expansions cause a heterogeneous group of severe neurological and neuromuscular disorders, including Huntingtonʼs disease, myotonic dystrophy, fragile X syndrome, and Friedreichʼs ataxia. The clinical management of these conditions critically depends on accurate characterization of repeat length, somatic mosaicism, internal sequence interruptions, and epigenetic modifications. However, conventional diagnostic approaches face fundamental limitations in resolving large, GC-rich, or structurally complex alleles. This review examines the evolving landscape of STR diagnostics, focusing on the emerging field of biosensor platforms. We critically evaluate the technical and biological challenges posed by polymerase slippage, secondary structure formation, somatic mosaicism, and allele dropout. We also assess biosensor platforms – including electrochemical impedance sensors, CRISPR-Cas systems (notably the REPLICA platform employing Cas3-mediated collateral activity) – have achieved femtomolar to attomolar limits of detection, enabling rapid point-of-care triage. We discuss the analytical principles, performance characteristics, and clinical applicability of these technologies. Finally, we propose a future diagnostic paradigm integrating biosensor-based rapid screening with targeted long-read sequencing for definitive characterization. This synergistic two-tiered strategy could to combine the accessibility and speed of point-of-care diagnostics with the comprehensive analytical power of third-generation sequencing, paving the way for precision medicine in repeat expansion disorders.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}