Review
Biochemistry & Molecular Biology
Shreyas P. Vaidya, Shubhankar Gadre, Ravi Teja Kamisetti, Malay Patra
Summary: The rapid increase in the global cancer burden poses significant challenges to society, requiring faster diagnosis and treatment methods. Small-molecule "theranostic" agents that combine diagnosis and therapy have advantages over purely therapeutic or diagnostic agents.
BIOSCIENCE REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Shubhankar Gadre, M. Manikandan, Prakash Duari, Sushant Chhatar, Astha Sharma, Subhash Khatri, Jyoti Kode, Madan Barkume, Nirmal Kumar Kasinathan, Manasi Nagare, Meena Patkar, Arvind Ingle, Mukesh Kumar, Ullas Kolthur-Seetharam, Malay Patra
Summary: This article introduces two designed heterobimetallic platinum (II)-ferrocene hybrids, showing multi-pronged anticancer action, especially crucial in circumventing apoptosis resistance and improving platinum cross resistance profile.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Multidisciplinary Sciences
Alessandra Rodriguez y Baena, Smrithi Rajendiran, Bryce A. Manso, Jana Krietsch, Scott W. Boyer, Jessica Kirschmann, E. Camilla Forsberg
Summary: These new mouse models allow for specific induction of death in hematopoietic cells or HSCs, providing a new platform to study HSC performance under steady-state conditions. These models can be used to test the necessity of HSCs for long-term hematopoiesis in vivo, as well as to explore the mechanisms regulating HSC engraftment and hematopoietic homeostasis.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Celeste Giansanti, Valentina Manzini, Antje Dickmanns, Achim Dickmanns, Maria Dilia Palumbieri, Andrea Sanchi, Simon Maria Kienle, Sonja Rieth, Martin Scheffner, Massimo Lopes, Matthias Dobbelstein
Summary: The MDM2 oncoprotein antagonizes p53 and sustains DNA replication fork progression, even in the absence of functional p53. This study demonstrates that MDM2 binds, inhibits, ubiquitinates, and destabilizes PARP1, resulting in accelerated fork progression. MDM2 also reduces fork reversal frequency, increases micronuclei occurrence, and exacerbates cell death, resembling the effects of PARP inhibition. These findings suggest that high MDM2 levels may represent a vulnerability of cancer cells.
Article
Biochemistry & Molecular Biology
Diego Dibitetto, Shannon Marshall, Andrea Sanchi, Martin Liptay, Jumana Badar, Massimo Lopes, Sven Rottenberg, Marcus B. Smolka
Summary: DNA-PKcs kinase plays a crucial role in the repair of DNA double-strand breaks and the control of fork dynamics. It promotes fork reversal, stabilizes stressed replication forks, and protects genome integrity. Inhibiting DNA-PKcs can restore chemotherapy sensitivity in BRCA2-deficient tumors.
Article
Biochemistry & Molecular Biology
Kurt Jacobs, Cyril Doerdelmann, Jana Krietsch, Daniel Gonzalez-Acosta, Nicolas Mathis, Saul Kushinsky, Estrella Guarino, Carmen Gomez-Escolar, Dolores Martinez, Jonas A. Schmid, Peter J. Leary, Raimundo Freire, Almudena R. Ramiro, Christine M. Eischen, Juan Mendez, Massimo Lopes
Summary: The mechanisms linking stem cell division to tumorigenesis are still not well understood. This study reveals that DNA damage associated with hematopoietic stem and progenitor cell proliferation induced by simulated viral infection is restricted to hematopoietic stem cells and these cells can rewire their DNA damage response. Further experiments demonstrate that fine-tuning the plasticity of replication forks is essential for supporting stem cell functionality during proliferation stimuli.
Article
Biophysics
Tina Leontidou, Ziyi Yu, Jeannine Hess, Katrin Geisler, Alison G. Smith, Anthony Coyne, Chris Abell
Summary: We demonstrate the generation of novel composite hydrogel microparticles loaded with BODIPY 505/515, which can be used to deliver the dye to microalgal cells to stain the intracellular lipids. The microparticles were prepared by combining polymeric micelles with hydrogel technology to obtain microparticles of enhanced loading capacity. The method can also be used to stain other types of microalgal cells.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Review
Biochemistry & Molecular Biology
Shreyas P. Vaidya, Malay Patra
Summary: Cancer, a major global health issue, is currently mainly treated with cytotoxic chemotherapy drugs, but their lack of cancer selectivity leads to increased side effects. Glycoconjugation has emerged as a strategy to improve drug selectivity and pharmacokinetics. This review provides an overview of this strategy and its application using platinum-based glycoconjugates, highlighting important aspects for further research.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
M. Manikandan, Shubhankar Gadre, Sushanta Chhatar, Gourav Chakraborty, Naushad Ahmed, Chinmoy Patra, Malay Patra
Summary: In this study, a ruthenium-ferrocene bimetallic agent and its analogues were designed, synthesized, and evaluated. These hybrid agents showed promising in vitro antitumor effects and could potentially overcome the resistance and side effects of platinum drugs. The study also revealed that the hybrid agent induced cell death through binding to biomolecules and generating reactive oxygen species.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Thomas W. Rees, Po-Yu Ho, Jeannine Hess
Summary: Antimicrobial resistance (AMR) is a significant global problem, causing over 1 million deaths in 2019 alone. Antimicrobial photodynamic therapy (aPDT) is a promising solution that uses photosensitizers activated by light to selectively target and kill bacteria. Metal complex photosensitizers have emerged as a potential tool in aPDT due to their excellent optoelectronic properties. This review summarizes the progress made in the last five years in the development of small-molecule metal complex photosensitizers for aPDT.
Article
Chemistry, Physical
Gauri S. Malankar, Divyesh S. Shelar, M. Manikandan, Malay Patra, Sudesh T. Manjare
Summary: A NSe2 chelating moiety embedded BOPHY probe was synthesized and characterized, showing high selectivity and sensitivity for Cu(II) detection. The probe rapidly reacted with Cu(II) in less than 1 second, resulting in a 6 fold increase in fluorescence intensity. It exhibited a detection limit of 10.8 nM and a 1:1 binding ratio of the complex (Probe:Cu(II)) according to the Job's plot. Furthermore, the probe demonstrated reversibility with S2- ions and was capable of sensitive detection of Cu(II) in live HeLa cells, showing strong green fluorescence.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Henriette Stoy, Katharina Zwicky, Danina Kuster, Kevin S. Lang, Jana Krietsch, Magdalena P. Crossley, Jonas A. Schmid, Karlene A. Cimprich, Houra Merrikh, Massimo Lopes
Summary: The authors developed an EM-based method to visualize R-loops directly, finding that DNA:RNA hybrids accumulate behind replication forks and affect fork slowing and reversal in transcription-replication conflicts. Previous studies on R-loops obstructing replication fork progression lacked direct visualization and non-ambiguous research tools. This study directly visualized estrogen-induced R-loops on the human genome using EM and measured their frequency and size at the single-molecule level. Combining EM and immuno-labeling in bacterial head-on TRCs, DNA:RNA hybrids were frequently observed behind replication forks, impacting fork behavior in conflict regions.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Microbiology
Jessica E. Waters, Lars Stevens-Cullinane, Lukas Siebenmann, Jeannine Hess
Summary: The increasing problem of antimicrobial resistance (AMR) is a major global threat to public health. Due to the lack of economic incentives and a decrease in the supply of new drugs in clinical pipelines, there is an urgent need for more innovative approaches to novel drug design and development. Metal-based compounds are emerging as a promising alternative to organic drugs, as they possess unique metal-specific modes of action against pathogens. This review highlights recent advances in metal-based antibacterial agents, including metal complexes, metal ions, and catalytic metallodrugs. The perspectives on the rational design of metal-based antibiotics and their potential in combating AMR are also discussed.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Divyesh S. Shelar, Gauri S. Malankar, M. Manikandan, Malay Patra, Ray J. Butcher, Sudesh T. Manjare
Summary: The first organoselenium-containing BOPPY-based small molecular probe was synthesized and its structure was analyzed. The probe exhibited high selectivity and sensitivity towards hypochlorite ions, and was successfully used for detecting endogenous hypochlorite in human cells. Additionally, the probe showed reversibility with biothiols.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Gauri S. Malankar, Divyesh S. Shelar, M. Manikandan, Malay Patra, Ray J. Butcher, Sudesh T. Manjare
Summary: In this study, a BOPHY-based organotellurium-containing probe was synthesized and characterized for the selective and sensitive detection of Hg2+ over other metal ions. The probe showed a rapid response time of less than 1 second and a 2.5-fold increase in fluorescent intensity upon detection of Hg2+. It demonstrated nanomolar detection capability (62 nM) and reversibility with S2- ions. The probe's sensitivity for detecting Hg2+ was confirmed in living HeLa cells.
DALTON TRANSACTIONS
(2022)
