Article
Multidisciplinary Sciences
Anastassia A. Vorobieva, Paul White, Binyong Liang, Jim E. Horne, Asim K. Bera, Cameron M. Chow, Stacey Gerben, Sinduja Marx, Alex Kang, Alyssa Q. Stiving, Sophie R. Harvey, Dagan C. Marx, G. Nasir Khan, Karen G. Fleming, Vicki H. Wysocki, David J. Brockwell, Lukas K. Tamm, Sheena E. Radford, David Baker
Summary: Through computational design, researchers successfully developed novel TMBs with no homology to known TMBs, which can reversibly insert and fold into synthetic lipid membranes, and exhibit experimental structures highly similar to computational models. This advancement is expected to facilitate the custom design of pores for various applications.
Article
Biochemistry & Molecular Biology
Kavita Singh, Sourav Sagar Behera, Rajdeep Tyagi, Ghanshyam Tiwari, Ram Sagar
Summary: A metal free synthesis of enantiopure 2,3-dideoxy-α, β-unsaturated carbohydrate enals (Perlin aldehydes) in CH3CN-0.02 N H2SO4 in water (1:1, v/v) with additives has been reported. The protocol works well for acetylated glycals, providing Perlin aldehydes and hemiacetals in good yields. The use of 0.02 N H2SO4 in water: acetonitrile (1:1, v/v) solvent system is essential for Perlin aldehyde formation.
CARBOHYDRATE RESEARCH
(2023)
Article
Nanoscience & Nanotechnology
Keisuke Shimizu, Batsaikhan Mijiddorj, Masataka Usami, Ikuro Mizoguchi, Shuhei Yoshida, Shiori Akayama, Yoshio Hamada, Akifumi Ohyamas, Kenji Usui, Izuru Kawamura, Ryuji Kawano
Summary: A de novo designed peptide with a beta-hairpin structure is able to assemble into beta-barrelled nanopores for single-molecule detection of polynucleotides and polypeptide chains. By manipulating amino acid sequences, artificial proteins and peptides with desired functionality can be developed. Redesigning the peptide to create monodisperse pores allows for detection of single polypeptide chains, showing potential for creating artificial nanopores adjustable to target molecules.
NATURE NANOTECHNOLOGY
(2022)
Article
Chemistry, Organic
HtooTint Wai, Thomas Koelblen, Matthew E. Hayes, Thomas P. Burris, Glenn C. Micalizio
Summary: Progress has been made in the asymmetric synthesis of euphanes, and a C14-desmethyl euphane system with five differentially substituted and electronically distinct alkenes has been successfully prepared. The route employed involves sequential metallacycle-mediated annulative cross-coupling, double asymmetric Bronsted acid mediated intramolecular Friedel-Crafts alkylation, and an oxidative rearrangement to establish the required C10 quaternary center. These studies have also led to the discovery of a novel euphane-based modulator of the Liver X Receptor.
Review
Oncology
Claudia Piombino, Marco Oltrecolli, Elena Tonni, Marta Pirola, Rossana Matranga, Cinza Baldessari, Stefania Pipitone, Massimo Dominici, Roberto Sabbatini, Maria Giuseppa Vitale
Summary: De novo metastatic hormone-sensitive prostate cancer usually has a poor prognosis, but recent advancements in new hormonal agents and combination therapy have slightly improved outcomes. Ongoing clinical trials are exploring new therapeutic approaches and personalized treatment options based on genomic features and biomarker-guided treatment.
Article
Biochemistry & Molecular Biology
Akihiro Ishiwata, Kiyotaka Fujita, Shinya Fushinobu, Katsunori Tanaka, Yukishige Ito
Summary: Methyl beta-L-arabinofuranosyl-(1 -> 2)-, -(1 -> 3)-, and -(1 -> 5)-alpha-L-arabinofuranosides have been stereoselectively synthesized using the NAP-IAD method. The substrate specificity of HypBA1 and XeHypBA1 on the different disaccharide linkages was studied, showing that HypBA1 has lower activity on beta-(1 -> 5)-linked disaccharide and XeHypBA1 has higher specificity on beta-(1 -> 2)-linked disaccharide.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biology
Shuangying Jiang, Yuanwei Tang, Liang Xiang, Xinlu Zhu, Zelin Cai, Ling Li, Yingxi Chen, Peishuang Chen, Yuge Feng, Xin Lin, Guoqiang Li, Jafar Sharif, Junbiao Dai
Summary: Synthetic genomics has opened new avenues for the functional study of viral and microbial genomes, as well as providing a method for constructing larger genomes of higher organisms. The study introduces an efficient pipeline for constructing large DNA fragments and describes a scar-free engineering method for assembling sequences. This method offers a standard framework for producing long DNA molecules crucial for synthetic genomics and metabolic engineering.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
David Baker, Stacey R. Gerben, Andrew J. Borst, Derrick R. Hicks, Isabelle Moczygemba, David Feldman, Brian Coventry, Wei Yang, Asim K. Bera, Marcos Miranda, Alex Kang, Hannah Nguyen
Summary: A challenge in designing protein-small-molecule recognition is the destabilization of protein monomers when incorporating cavities suitable for specific recognition. We overcome this challenge by designing binding pockets at off-axis sites on homo-oligomers, allowing for general recognition of asymmetric substrates. Through computational design, we have successfully created proteins with non-symmetrical interfaces that can bind small molecules, providing new possibilities for binding design free from monomer destabilization constraints.
Article
Multidisciplinary Sciences
Xingqing Xiao, Yiming Wang, Dillon T. Seroski, Kong M. Wong, Renjie Liu, Anant K. Paravastu, Gregory A. Hudalla, Carol K. Hall
Summary: A computational and experimental approach is used to design pairs of charge-complementary peptides for controllable fabrication of multicomponent biomaterials. Selective coassembly of these pairs into beta-sheet nanofibers or nonfibrillar aggregates is demonstrated through biophysical experiments, showcasing the potential for functional biomaterial design. Solid-state NMR analysis suggests that the designed peptides exhibit a higher degree of structural order compared to previously reported peptides.
Article
Biochemistry & Molecular Biology
Areetha D'Souza, Surajit Bhattacharjya
Summary: The field of de novo protein design has achieved significant success over the past few decades, particularly in designing functional beta-sheets that bind heme. By optimizing beta-hairpin peptides and multistranded beta-sheets, researchers have developed proteins capable of peroxidase activity, catalysis, and electron transfer in both aqueous and membrane-like environments. This progress highlights the potential for designing diverse functions in beta-sheet proteins through de novo design.
Article
Multidisciplinary Sciences
Arunima Mishra, Irena Cosic, Ivan Loncarevic, Drasko Cosic, Hansel M. Fletcher
Summary: Antimicrobial resistance is a global public health concern that requires new treatments, especially for multidrug-resistant bacteria. This study used the Resonant Recognition Model to evaluate the structure-function properties of beta-lactamase proteins and designed peptides as inhibitors, showing promising results.
Editorial Material
Chemistry, Multidisciplinary
Lijun Quan, Tingfang Wu, Qiang Lyu
Summary: This article discusses the importance of proteins as the foundation of life, specifically focusing on the significance of secondary structures for protein functioning. Buehler and his team introduce deep learning models to generate novel proteins with specific secondary structure constraints, likening it to constructing a functional house based on desired keystones.
Article
Biochemistry & Molecular Biology
Anasuya Moitra, Vitasta Tiku, Doron Rapaport
Summary: Mitochondrial outer membrane beta-barrel proteins, including artificial proteins, are targeted to and integrated into the outer membrane in yeast cells, independent of import receptors, but with a strong dependency on the TOB/SAM complex.
Review
Chemistry, Multidisciplinary
Sugyeom Kim, Jeremy Oiler, Yalan Xing, George A. O'Doherty
Summary: The development and application of asymmetric synthesis of oligosaccharides from achiral starting materials are reviewed in this article. This approach involves the use of asymmetric catalysis to synthesize optically pure furan alcohols, in combination with Achmatowicz oxidative rearrangement for the synthesis of various pyranones. Additionally, diastereoselective palladium-catalyzed glycosylation and subsequent diastereoselective post-glycosylation transformation are used for the synthesis of oligosaccharides.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Na Liu, Lian Wu, Jinhui Feng, Xiang Sheng, Jian Li, Xi Chen, Jianjiong Li, Weidong Liu, Jiahai Zhou, Qiaqing Wu, Dunming Zhu
Summary: This study reported the crystal structures of a l-erythro-3,5-diaminohexanoate dehydrogenase and its variants, the only known member of beta-AADH family, revealing differences in substrate binding and catalytic mechanism compared to alpha-AADHs. Engineered variants with improved activity towards various aliphatic beta-amino acids were obtained, allowing for the preparation of beta-amino acids with excellent enantioselectivity and high yields. These results provide insights into the molecular mechanism of 3,5-DAHDH and lay a solid foundation for further design of beta-AADHs for asymmetric synthesis of beta-amino acids.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Inorganic & Nuclear
Domenico Loreto, Anna Esposito, Nicola Demitri, Annalisa Guaragna, Antonello Merlino
Summary: The study synthesized and analyzed a cis-Rh-2(OAc)(2)(tfa)(2) complex and its interaction with proteins, revealing differences in reactivity compared to Rh-2(OAc)(4) when binding to proteins.
DALTON TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Hoai Nguyen, Mikhail Abramov, Jef Rozenski, Elena Eremeeva, Piet Herdewijn
Summary: Chemically modified nucleic acids are of great interest in synthetic biology for creating a regulatable and sophisticated synthetic system. Researchers have successfully synthesized modified DNA sequences and introduced them into eukaryotic cells, which is important for scientists working in the field of xenobiology in yeast.
Article
Chemistry, Organic
Anna Esposito, Giovanni Talarico, Maria De Fenza, Daniele D'Alonzo, Annalisa Guaragna
Summary: The Tsuji-Trost reaction of cyclopentenyl carbonates was investigated for the stereoconvergent synthesis of cyclopentenyl nucleosides. Changes in catalyst amount were found to selectively lead to the synthesis of cis configured cyclopentenyl N9-linked purine nucleosides, regardless of the relative configuration of the starting substrates. DFT studies provided insights into the low activation energy associated with the crucial inversion step.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Maria De Fenza, Anna Esposito, Giovanni Talarico, Graciela Andrei, Robert Snoeck, Daniele D'Alonzo, Annalisa Guaragna
Summary: In this study, six-membered nucleoside analogues with a piperidine ring as the preorganized (deoxy)ribose bioisostere were synthesized and evaluated for their antiviral activity. The 5-iododeoxyuridine analogue showed activity against all tested DNA viruses. DFT analysis and pH-dependent NMR experiments suggested that the antiviral activity was attributed to the biomimetic character of the piperidine ring, which can mimic the conformation of natural nucleosides when interacting with viral enzymes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Niklas Freund, Alexander Taylor, Sebastian Arangundy-Franklin, Nithya Subramanian, Sew-Yeu Peak-Chew, Amy M. Whitaker, Bret D. Freudenthal, Mikhail Abramov, Piet Herdewijn, Philipp Holliger
Summary: In this study, a two-residue "gate" was discovered in an archaeal DNA polymerase, which enables the synthesis of 2'-modified RNA oligomers. This discovery expands the application potential of 2'-modified RNA in nucleic acid therapeutics and biotechnology.
Article
Microbiology
Leah Goulding, Eleonora Kiss, Robert Vrancken, Nesya Goris, Min Luo, Elisabetta Groaz, Piet Herdewijn, Linda Dixon
Summary: African swine fever virus is a highly contagious hemorrhagic viral disease that causes significant losses in the domestic pig population. Since there are currently no vaccines available, finding effective antiviral agents is crucial. This study identified two compounds that can effectively inhibit the replication of African swine fever virus, showing potential as prophylactic and therapeutic agents.
Article
Chemistry, Medicinal
Valeria De Pasquale, Anna Esposito, Gianluca Scerra, Melania Scarcella, Mariangela Ciampa, Antonietta Luongo, Daniele D'Alonzo, Annalisa Guaragna, Massimo D'Agostino, Luigi Michele Pavone
Summary: Sanfilippo syndrome is a group of genetic diseases characterized by the accumulation of heparan sulfate (HS) in lysosomes and other cellular compartments, leading to tissue and organ dysfunctions. This study found that N-substituted L-iminosugars can reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and a neuronal cellular model of Sanfilippo B subtype. These compounds also increase the levels of defective enzyme alpha-N-acetylglucosaminidase and correct its sorting, as well as reduce HS accumulation by downregulating protein levels of exostosin glycosyltransferases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shenghua Gao, Letian Song, Hongtao Xu, Antonios Fikatas, Merel Oeyen, Steven De Jonghe, Fabao Zhao, Lanlan Jing, Dirk Jochmans, Laura Vangeel, Yusen Cheng, Dongwei Kang, Johan Neyts, Piet Herdewijn, Dominique Schols, Peng Zhan, Xinyong Liu
Summary: DF-47 and DF-51 were identified as effective inhibitors of SARS-CoV-2/DENV polymerase through RdRp inhibition screening and in vitro antiviral study. In silico simulation revealed stable binding modes between DF-47/DF-51 and SARS-CoV-2/DENV RdRp, including chelating with Mg2+ near the polymerase active site. These polyphenols have the potential to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with a new scaffold.
Article
Biochemistry & Molecular Biology
Lauriane Rietmeyer, Ines Li de la Sierra-Gallay, Guy Schepers, Delphine Dorchene, Laura Iannazzo, Delphine Patin, Thierry Touze, Herman van Tilbeurgh, Piet Herdewijn, Melanie Etheve-Quelquejeu, Matthieu Fonvielle
Summary: Xenobiotic nucleic acids (XNAs) have great potential in synthetic biology, biotechnology, and molecular medicine. However, their ability to mimic nucleic acids needs further exploration. In this study, we synthesized three L-Ala-tXNAs analogs to investigate their ability to mimic tRNA. We found that L-Ala-tXNAs containing HNA or 2' F-RNA could be substrates of a bacterial Fem transferase. The synthesis of peptidyl-XNA and its binding with the enzyme demonstrated the impact of XNA on protein binding. This is the first report of functional tXNA in an in vitro assay, suggesting the potential of using tXNA as a substitute for tRNA in translation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Hui Yang, Elena Eremeeva, Mikhail Abramov, Maarten Jacquemyn, Elisabetta Groaz, Dirk Daelemans, Piet Herdewijn
Summary: An enzymatic method was developed to generate partially base-modified RNA constructs, as well as fully modified RNA constructs featuring multiple modified bases. The efficiency of the fully modified RNA constructs was enhanced by using different T7 RNA polymerase variants. The study also demonstrated the successful incorporation of modified bases into PCR products and the effectiveness of the modified RNA constructs in CRISPR-Cas9 cleavage assays.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Cecile Gasse, Puneet Srivastava, Guy Schepers, Joachim Jose, Marcel Hollenstein, Philippe Marliere, Piet Herdewijn
Summary: Chemical cell surface modification is an important field with great potential in tissue engineering, cell-based immunotherapy, and regenerative medicine. However, research on engineering bacterial tissues through chemical cell surface modification is lacking, especially in finding suitable molecular handles. In this study, a novel strategy using orthogonal nucleic acid-protein conjugation was developed to induce artificial bacterial aggregation. This system combines the selective and stable linkage of a protein Tag at the cell surface with the modularity and reversibility of aggregation through oligonucleotide hybridization. The immobilization of XNA via covalent, SNAP-tag-mediated interactions on cell surfaces for bacterial aggregation is reported for the first time.
Article
Biochemistry & Molecular Biology
Pradeep S. Pallan, Terry P. Lybrand, Eriks Rozners, Mikhail Abramov, Guy Schepers, Elena Eremeeva, Piet Herdewijn, Martin Egli
Summary: Efforts are being made to create and implement alternative genetic systems with pairing components orthogonal to natural base pairs. Another approach conserves Watson-Crick pairing but substitutes one or all of the four letters of the DNA alphabet with modified components. This study analyzes the properties of a DZA DDD structure and reveals interesting findings regarding stability, hydration, structure, and dynamics.
Article
Biochemistry & Molecular Biology
Peter Schofield, Alexander Taylor, Jerome Rihon, Cristian D. Pena Martinez, Sacha Zinn, Charles-Alexandre Mattelaer, Jennifer Jackson, Gurpreet Dhaliwal, Guy Schepers, Piet Herdewijn, Eveline Lescrinier, Daniel Christ, Philipp Holliger
Summary: Nucleic acids serve as the basis of heredity and are increasingly utilized to create novel nanostructures, devices, and drugs. Chemically modified alternatives, known as xeno nucleic acids (XNAs), have been developed to expand their chemical and functional capabilities. XNA aptamers, which can bind targets with high affinity and specificity, have not been thoroughly investigated in terms of their structure and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mengmeng Wang, Kunyu Qu, Peipei Zhao, Xin Yin, Yiwei Meng, Piet Herdewijn, Chao Liu, Lixin Zhang, Xuekui Xia
Summary: Gemcitabine prodrugs with modifications on the 4-N-amino group by employing an acetylated L- or D-lysine moiety masked by different substitutions were synthesized. These prodrugs showed higher anticancer activity than gemcitabine in A549 lung cells and exhibited potent activity against BxPC-3 pancreatic cells. They also showed lower toxicity towards normal cells and improved stability in various metabolic environments. Overall, acetylated lysine conjugated gemcitabine prodrugs could be promising leads for new anticancer drugs.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Valeria De Pasquale, Anna Esposito, Gianluca Scerra, Melania Scarcella, Mariangela Ciampa, Antonietta Luongo, Daniele D'Alonzo, Annalisa Guaragna, Massimo D'Agostino, Luigi Michele Pavone
Summary: Sanfilippo syndrome is a group of genetic diseases caused by a lack or decreased activity of enzymes involved in heparan sulfate catabolism. This leads to the accumulation of heparan sulfate in cells, resulting in tissue and organ dysfunctions, including severe neurodegeneration. In this study, N-substituted L-iminosugars were found to significantly reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and a neuronal cellular model of Sanfilippo B subtype. They also corrected the sorting of defective alpha-N-acetylglucosaminidase and reduced heparan sulfate accumulation by downregulating exostosin glycosyltransferases. These findings suggest a promising pharmacological potential for these glycomimetics in treating Sanfilippo syndrome.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
