Demands on modern combinatorial chemistry have necessitated massive investment in new synthetic technologies that will allow the production of highly pure drug candidates on short timescales. The advent of microfluidic reactor technologies has recently provided a new tool for the combinatorial chemist, offering the promise of ultra-high-throughput solution-phase chemistries. This review describes why such microscale systems provide unique environments for performing high-efficiency molecular synthesis, details some of the most important recent developments in the field and assesses the true applicability of micro-engineered reactors in high-throughput compound synthesis.
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Comb Chem High Throughput Screen
January 2025
APIGENEX s.r.o., Poděbradská 173/5, Prague 19000, Czech Republic.
Objective: In search of efficient anticancer agents, we aimed at the design and synthesis of a library of tetrasubstituted alkenes. These are structural analogues of tamoxifen, one of the widely used anticancer therapeutics.
Methods: Our small organic compound library was prepared via a chemical synthesis in the solution using the Larock three-component coupling reaction, which is known to tolerate diverse functional groups.
Org Biomol Chem
January 2025
Department of Chemistry, University of Turku, Henrikinkatu 2, 20500 Turku, Finland.
In this article, a neoacetalization-based method for post-SELEX modification of aptamers is introduced. Three modified quinine binding aptamer scaffolds were synthesized by replacing three different nucleosides of the binding site with a (2,3)-4-(methoxyamino)butane-1,2,3-triol residue. These aptamer scaffolds were incubated in different aldehyde mixtures with and without quinine, allowing the reversible formation of -methoxy-1,3-oxazinane (MOANA) nucleoside analogues through dynamic combinatorial chemistry.
View Article and Find Full Text PDFChem Sci
December 2024
State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian 116023 P. R. China
Small ubiquitin-like modifier (SUMO) plays a pivotal role in diverse cellular processes and is implicated in diseases such as cancer and neurodegenerative disorders. However, large-scale identification of endogenous SUMO-1 faces challenges due to limited enrichment methods and its lower abundance compared to SUMO-2/3. Here we propose a novel combinatorial peptide strategy, combined with anti-adhesive polymer development, to enrich endogenous SUMO-1 modified peptides, revealing a comprehensive SUMOylation landscape.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central Asia, School of Medical Engineering and Technology Xinjiang Medical University, Urumqi, 830011, People's Republic of China.
Purpose: A synergistic treatment strategy of phototherapy and chemotherapy has been shown to improve efficacy and offer unique advantages over monotherapy. The purpose of this study is to explore a new nanocarrier system with liposome as the inner membrane and erythrocyte membrane as the outer membrane, which aims to realize the leak-free load of phototherapy drug indocyanine green (ICG) and chemotherapy drug doxorubicin (DOX), prolong the circulation time in vivo and improve the therapeutic effect.
Patients And Methods: In this study, bilayer membrane-loaded ICG and DOX nanoparticles (RBC@ICG-DOX NPs) were prepared and characterized.
Biotechnol Bioeng
January 2025
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Human pluripotent stem cells (hPSCs) can be differentiated in vitro to an increasing number of mature cell types, presenting significant promise for addressing a wide range of diseases and studying human development. One approach to further enhance stem cell differentiation methods would be to coordinate multiple inducible gene or protein switches to operate simultaneously within the same cell, with minimal cross-interference, to precisely regulate a network of lineage-specifying transcription factors (TFs) to guide cell fate decisions. Therefore, in this study, we designed and tested various mammalian gene and protein switches responsive to clinically safe small-molecule inhibitors of viral proteases.
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