Article
Chemistry, Medicinal
Milan Dejmek, Andrea Brazdova, Tomas Otava, Marketa Pimkova Polidarova, Martin Klima, Miroslav Smola, Zdenek Vavrina, Milos Budesinsky, Martin Dracinsky, Radek Liboska, Evzen Boura, Gabriel Birkus, Radim Nencka
Summary: CDNs activate the cGAS-STING pathway, which plays a vital role in immunomodulation against infections, cell damage, and cancer. A novel class of CDNs containing vinylphosphonate showed high anti-tumor activity both in vitro and in vivo, and the crystal structure of the ligand bound to the STING protein was solved. These findings validate the therapeutic potential of vinylphosphonate CDNs and offer opportunities for drug development in cancer immunotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
C. Johnston, C. Hardacre, M. E. Migaud
Summary: Liquid-assisted mechanochemistry has been investigated as a versatile approach for coupling nucleoside phosphoramidite with 5'-OH partially protected nucleoside. Advantages include simplified reaction protocol, reduction in toxic solvents, improved mixing of solid reagents for mechanochemical reactions, and low hydrolytic product formation.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Review
Biotechnology & Applied Microbiology
Tabea Bartsch, Martin Becker, Jascha Rolf, Katrin Rosenthal, Stephan Lutz
Summary: Cyclic dinucleotides (CDNs), as strong agonists of the stimulator of interferon genes, have great potential in pharmaceutical applications. The synthesis of CDNs through chemical and biocatalytic methods has its advantages and challenges. This review discusses the latest discoveries and trends in CDN synthesis, with a focus on the most promising biotechnological processes for CDN production.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Immunology
Sudhanshu Mudgal, Kasi Manikandan, Ahana Mukherjee, Anuja Krishnan, Krishna Murari Sinha
Summary: Cyclic dinucleotides play important physiological and pathophysiological roles in bacteria, regulating various cellular processes. cdA, predominantly found in gram-positive bacteria, is synthesized and hydrolyzed to control cellular functions through different mechanisms.
MICROBIAL PATHOGENESIS
(2021)
Article
Biochemistry & Molecular Biology
Zhenghua Wang, Cancan Zhao, Chuanlin Wang, Hang Zhang, Dejun Ma, Qiangzhe Zhang, Xin Wen, Luyuan Li, Zhen Xi
Summary: Inosine-containing CDNs have the potential to activate all five major hSTING variants, showing promise as novel immune therapy activators. Molecular dynamic simulations and ITC assays further confirm the interaction mechanisms, providing insights for future drug development.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Dorothee Vicogne, Nicolas Beauval, Zoe Durin, Delphine Allorge, Kateryna Kondratska, Aurelien Haustrate, Natasha Prevarskaya, Vladimir Lupashin, Dominique Legrand, Francois Foulquier
Summary: TMEM165 is a cation transporter critical for Golgi glycosylation and cellular manganese homeostasis. Its deficiency leads to glycosylation defects, which can be restored by manganese supplementation. This study reveals the importance of TMEM165 in maintaining Golgi manganese homeostasis and cellular manganese detoxification through the activity of SPCA1.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Natalia Kleczewska, Pawel J. Sikorski, Zofia Warminska, Lukasz Markiewicz, Renata Kasprzyk, Natalia Baran, Karina Kwapiszewska, Aneta Karpinska, Jaroslaw Michalski, Robert Holyst, Joanna Kowalska, Jacek Jemielity
Summary: Targeting cap-dependent translation initiation is a potential approach for developing novel anti-cancer therapies. Synthetic cap analogs are potent antagonists of eIF4E and delivery into cells can be facilitated by small molecule ligands like cholesterol, which also enhances interactions with eIF4E and shows cytotoxic effects towards cancer cells.
Article
Pharmacology & Pharmacy
Xin Sun, Yun Ni, Yanpu He, Mengdi Yang, Tetsuo Tani, Shunsuke Kitajima, David A. Barbie, Jiahe Li
Summary: The STING pathway activated by CDNs is explored for its potential in vaccine adjuvants and cancer immunotherapy. Protein-based carriers show promise in improving the delivery of STING agonists, with the engineered STING platform being effective in enhancing CDN delivery and restoring STING signaling in cells with impaired expression, providing a unique strategy for targeting STING-silenced tumors.
ADVANCED THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Miroslav Smola, Ondrej Gutten, Milan Dejmek, Milan Kozisek, Thomas Evangelidis, Zahra Aliakbar Tehrani, Barbora Novotna, Radim Nencka, Gabriel Birkus, Lubomir Rulisek, Evzen Boura
Summary: The study investigates the mechanism by which STING regulates immune responses, analyzing the factors contributing to the different affinities of CDNs ligands through structural and computational models. Experimental results suggest that the higher affinity of fluorinated analogues is due to smaller loss of entropy and strain energy upon binding.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Li Xu, Hongping Deng, Liang Wu, Dali Wang, Leilei Shi, Qiuhui Qian, Xiangang Huang, Lijuan Zhu, Xihui Gao, Jiapei Yang, Yue Su, Jing Feng, Xinyuan Zhu
Summary: A supramolecular nanodelivery system for STING agonist c-di-GMP was constructed using natural endogenous small molecules oleic acid and deoxycytidine. The resulting stable cyclic dinucleotide nanoparticles (CDG-NPs) promoted STING activation and tumor immunogenicity, enhancing STING-mediated anti-tumor immunity.
Article
Biology
Pan Cheng, Xin Zhao, Lizabeth Katsnelson, Elaine M. Camacho-Hernandez, Angela Mermerian, Joseph C. Mays, Scott M. Lippman, Reyna Edith Rosales-Alvarez, Raquel Moya, Jasmine Shwetar, Dominic Grun, David Fenyo, Teresa Davoli
Summary: This study reveals the regulation of RNA and protein abundance in genes with somatic copy number alterations (SCNAs), providing insights into gene regulation. Protein complex genes are primarily regulated at the protein level, while non-complex genes are primarily regulated at the RNA level. Interestingly, genes in the same pathway show similar levels of RNA and protein regulation, with certain pathways showing stronger regulation at either the protein level or the RNA level.
Article
Geriatrics & Gerontology
Kathleen A. Ross, April M. Tingle, Sujata Senapati, Kaitlyn G. Holden, Michael J. Wannemuehler, Surya K. Mallapragada, Balaji Narasimhan, Marian L. Kohut
Summary: Age-associated impairments of immune response and inflammaging may contribute to poor vaccine efficacy in older adults. Next generation vaccines may utilize biomaterials to enhance antigen presentation without inducing excessive inflammatory responses. In this study, novel biomaterials demonstrated a modest induction of cytokine secretion, suggesting their potential role in next generation vaccines for older adults.
Article
Chemistry, Applied
Annamalai Senthilvelan, Muthian Shanmugasundaram, Anilkumar R. Kore
Summary: An efficient and improved chemical method for gram-scale synthesis of RNA dinucleotides has been described. The method utilizes phosphoramidite chemistry and a solution-phase strategy, resulting in high yields and purity (> 99.5%).
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Review
Chemistry, Medicinal
Mengdi Shang, Kuan Lu, Wenli Guan, Shujie Cao, Mengtian Ren, Chuanzheng Zhou
Summary: The cGAS-STING pathway is a vital part of the innate immune system, with 2',3'-cGAMP serving as a key second messenger. Research on 2',3'-cGAMP analogues for immunotherapeutic potential has been increasingly popular over the past decade.
Article
Biochemistry & Molecular Biology
Zahra Aliakbar Tehrani, Lubomir Rulisek, Jiri Cerny
Summary: The study utilized molecular dynamics simulations to investigate the binding dynamics of natural CDNs with hSTINGwt protein, revealing that the interactions between CDN and protein are controlled by conformational changes and protein dynamics. Different CDNs induce varying degrees of conformational and dynamics changes in the ligand binding cavity of hSTINGwt, with implications for designing new compounds modulating hSTING activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Bruno Y. Matsuyama, Petya V. Krasteva, Claudine Baraquet, Caroline S. Harwood, Holger Sondermann, Marcos V. A. S. Navarro
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Microbiology
Raphael Laurenceau, Petya V. Krasteva, Amy Diallo, Sahra Ouarti, Magalie Duchateau, Christian Malosse, Julia Chamot-Rooke, Remi Fronzes
Article
Biochemistry & Molecular Biology
Amy Diallo, Hannah R. Foster, Katarzyna A. Gromek, Thomas N. Perry, Annick Dujeancourt, Petya V. Krasteva, Francesca Gubellini, Tanya G. Falbel, Briana M. Burton, Remi Fronzes
MOLECULAR MICROBIOLOGY
(2017)
Article
Multidisciplinary Sciences
Petya Violinova Krasteva, Joaquin Bernal-Bayard, Laetitia Travier, Fernando Ariel Martin, Pierre-Alexandre Kaminski, Gouzel Karimova, Remi Fronzes, Jean-Marc Ghigo
NATURE COMMUNICATIONS
(2017)
Article
Multidisciplinary Sciences
Parveen Goyal, Petya V. Krasteva, Nani Van Genven, Francesca Gubellini, Imke Van den Broeck, Anastassia Troupiotis-Tsailaki, Wim Jonckheere, Gerard Pehau-Arnaudet, Jerome S. Pinkner, Matthew R. Chapman, Scott J. Hultgren, Stefan Howorka, Remi Fronzes, Han Remaut
Editorial Material
Biochemical Research Methods
Petya V. Krasteva
Editorial Material
Biochemical Research Methods
Petya V. Krasteva
Editorial Material
Biochemical Research Methods
Petya V. Krasteva
Editorial Material
Biochemical Research Methods
Petya V. Krasteva
Article
Microbiology
Samira Zouhir, Wiem Abidi, Meryem Caleechurn, Petya Violinova Krasteva
Article
Genetics & Heredity
Ipek Altinoglu, Guillaume Abriat, Alexis Carreaux, Lucia Torres-Sanchez, Mickael Poidevin, Petya Violinova Krasteva, Yoshiharu Yamaichi
Summary: This study used a comparative proteomics approach to identify novel HubP partners in the opportunistic cholera pathogen Vibrio cholerae. The results revealed a more versatile role for HubP in cell polarization and identified new mechanisms of motility regulation. The findings provide new insights into the coevolution and functional interdependence of chemotactic signaling, bacterial motility, and biofilm formation.
Article
Multidisciplinary Sciences
Wiem Abidi, Marion Decossas, Lucia Torres-Sanchez, Lucie Puygrenier, Sylvie Letoffe, Jean-Marc Ghigo, Petya Krasteva
Summary: This study provides structural and mechanistic insights into the role of the accessory subunits BcsH and BcsD in determining crystalline BC secretion in the Gluconacetobacter lineage. The research reveals that oligomeric BcsH drives the assembly of BcsD into a supramolecular cytoskeletal scaffold, stabilizing the cellulose-extruding synthase nanoarrays through an unexpected inside-out mechanism for secretion system assembly.
Review
Microbiology
Wiem Abidi, Lucia Torres-Sanchez, Axel Siroy, Petya Violinova Krasteva
Summary: This review provides an overview of the current mechanistic knowledge on bacterial cellulose secretion, with a focus on the structure, assembly, and cooperativity of Bcs secretion system components.
FEMS MICROBIOLOGY REVIEWS
(2022)
Article
Multidisciplinary Sciences
Wiem Abidi, Samira Zouhir, Meryem Caleechurn, Stephane Roche, Petya Violinova Krasteva
Summary: This study reveals the assembly mechanism and cellulose secretion process of the Bcs secretion system through cryo-EM structures and crystallographic snapshots, as well as its unexpected subunit stoichiometry, multisite c-di-GMP recognition, and ATP-dependent regulation.