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30th Anniversary of Molecules—Recent Advances in Bioorganic Chemistry

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 537

Special Issue Editors


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Guest Editor
Department of Ecological and Biological Sciences, Tuscia University, 01100 Viterbo, Italy
Interests: organic chemistry; bioorganic chemistry; chemistry of natural substances and catalysis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemistry, University of Turku, 20014 Turku, Finland
Interests: kinetic studies on chemical models of ribonucleases and ribozymes; synthesis and application of oligonucleotide conjugates; pro-drug strategies for phosphoester drugs; novel approaches for medium-scale synthesis of oligonucleotides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2026 will mark the 30th anniversary of Molecules, and to celebrate this important milestone, we are pleased to announce the Special Issue entitled “30th Anniversary of Molecules—Recent Advances in Bioorganic Chemistry”, dedicated to highlighting cutting-edge research in the field of bioorganic chemistry.

Bioorganic chemistry lies at the interface of organic chemistry and the life sciences, focusing on the chemical principles underlying biological processes and the design, synthesis, and functional study of biologically relevant molecules. This interdisciplinary field encompasses the development of chemical tools to probe biological systems, the synthesis of complex biomolecules and biomimetic structures, and the exploration of molecular interactions that govern biological function and regulation.

The aim of this Special Issue is to showcase recent high-quality advances and emerging trends in bioorganic chemistry contributed by researchers from diverse scientific backgrounds. Particular emphasis is placed on molecular-level studies that deepen our understanding of enzyme function, catalysis, molecular recognition, biomolecular interactions, and the chemical basis of biological signaling and regulation.

Contributions to this Special Issue may include—but are not limited to—research on chemoenzymatic and biomimetic synthesis, biocatalysis and biosynthetic pathways, enzyme inhibitors and immobilization strategies, functional proteins and peptides, non-natural amino acids, glycobiology, bioactive lipids, nucleic acid recognition, neurotoxins and receptor interactions, immunochemical techniques, supramolecular and membrane chemistry, as well as advanced analytical and mass spectrometry-based studies of biomolecules. Both fundamental studies and applied research with clear biological or biomedical relevance are welcome.

We warmly invite researchers working across the broad and dynamic field of bioorganic chemistry to contribute their latest findings to this celebratory Special Issue, thereby helping to commemorate the 30-year legacy of Molecules and to shape its future scientific impact.

Prof. Dr. Raffaele Saladino
Prof. Dr. Harri Lönnberg
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bioorganic chemistry
  • chemoenzymatic synthesis
  • biocatalysis
  • biomimetic synthesis
  • biomolecular interactions
  • functional biomolecules
  • molecular recognition

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Published Papers (2 papers)

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Research

17 pages, 2499 KB  
Article
Inhibition of Histone Lysine Acetyltransferases by Coenzyme A Analogs
by Faidra Voukia, Nurgül Bilgin, Steffen Bundgaard Andersen and Jasmin Mecinović
Molecules 2026, 31(3), 477; https://doi.org/10.3390/molecules31030477 - 29 Jan 2026
Viewed by 143
Abstract
Histone lysine acetylation is a widespread posttranslational modification, essential for vital functions in eukaryotic organisms. Histone lysine acetyltransferases (KATs) employ acetyl-coenzyme A as a universal acetyl donor for acetylation of lysine residues in histone and non-histone proteins. Despite the biomedicinal importance of modulation [...] Read more.
Histone lysine acetylation is a widespread posttranslational modification, essential for vital functions in eukaryotic organisms. Histone lysine acetyltransferases (KATs) employ acetyl-coenzyme A as a universal acetyl donor for acetylation of lysine residues in histone and non-histone proteins. Despite the biomedicinal importance of modulation of the KAT activity, application of the acetyl-coenzyme A cosubstrate structure for the design of potent and selective inhibitors has been underexplored. Here, we developed functionalized coenzyme A analogs as inhibitors against human histone lysine acetyltransferases GCN5, KAT8, and HAT1. In contrast to the unmodified coenzyme A, which was found to be a poor inhibitor of GCN5 and KAT8 (IC50 > 150 μM), we showed that a ketone-substituted coenzyme A was the most potent inhibitor of GCN5 and KAT8 (IC50 = 10.9 μΜ and 13.6 μΜ, respectively). Coenzyme A and an acetamide-substituted coenzyme A efficiently inhibited HAT1 (IC50 = 7.3 μΜ and IC50 = 3.9 μΜ, respectively). Our work demonstrates that human KATs can be efficiently and selectively inhibited by S-functionalized coenzyme A, the results exhibiting significant potential towards development of highly active chemical probes for biomedically important KATs. Full article
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17 pages, 2175 KB  
Article
Efficient Degradation of Monoacylglycerols by an Engineered Aspergillus oryzae Lipase: Synergistic Effects of sfGFP Fusion and Rational Design
by Yuqing Wang, Fang Liu, Yuxi Tian, Jiazhen Sun, Dawei Liu, Fei Li, Yaping Wang and Ben Rao
Molecules 2026, 31(3), 398; https://doi.org/10.3390/molecules31030398 - 23 Jan 2026
Viewed by 246
Abstract
Monoacylglycerols (MAGs) are significant intermediate byproducts in the hydrolysis of oils and fats. The accumulation of MAGs not only reduces the quality and purity of the final products in biodiesel production and edible oil refining but also poses challenges for downstream separation processes. [...] Read more.
Monoacylglycerols (MAGs) are significant intermediate byproducts in the hydrolysis of oils and fats. The accumulation of MAGs not only reduces the quality and purity of the final products in biodiesel production and edible oil refining but also poses challenges for downstream separation processes. Therefore, the development of efficient biocatalysts for the specific MAG conversion is of great industrial importance. The lipase from Aspergillus oryzae (AOL) has shown potential for lipid modification; however, the wild-type enzyme (WT) suffers from poor solubility, tendency to aggregate, and low specific activity towards MAGs in aqueous systems, which severely restricts its practical application. In this study, a combinatorial protein engineering strategy was employed to overcome these limitations. We integrated fusion protein technology with rational design to enhance both the functional expression and catalytic efficiency of AOL. Firstly, the superfolder green fluorescent protein (sfGFP) was fused to the N-terminus of AOL. The results indicated that the sfGFP fusion tag significantly improved the solubility and stability of the enzyme, preventing the formation of inclusion bodies. The fusion protein sfGFP-AOL exhibited a MAG conversion rate of approximately 65%, confirming the positive impact of the fusion tag on enzyme developability. To further boost catalytic performance, site-directed mutagenesis was performed based on structural analysis. Among the variants, the mutant sfGFP-Y92Q emerged as the most potent candidate. In the MAG conversion, sfGFP-Y92Q achieved a conversion rate of 98%, which was not only significantly higher than that of sfGFP-AOL but also outperformed the widely used commercial immobilized lipase, Novozym 435 (~54%). Structural modeling and docking analysis revealed that the Y92Q mutation optimized the geometry of the active site. The substitution of Tyrosine with Glutamine at position 92 likely enlarged the substrate-binding pocket and altered the local electrostatic environment, thereby relieving steric hindrance and facilitating the access of the bulky MAG substrate to the catalytic center. In conclusion, this work demonstrates that the synergistic application of sfGFP fusion and rational point mutation (Y92Q) can dramatically transform the catalytic properties of AOL. The engineered sfGFP-Y92Q variant serves as a robust and highly efficient biocatalyst for MAG degradation. Its superior performance compared to commercial standards suggests immense potential for cost-effective applications in the bio-manufacturing of high-purity fatty acids and biodiesel, offering a greener alternative to traditional chemical processes. Full article
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