Article
Medicine, Research & Experimental
Andrea Gilg, Mirja Harms, Lia-Raluca Olari, Ann-Kathrin Urbanowitz, Halvard Bonig, Jan Muench
Summary: Medicinal HSA preparations do not contain EPI-X4, but can replenish its precursor which may be cleaved to EPI-X4 under appropriate environmental conditions.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Lisa Marie Kaiser, Mirja Harms, Daniel Sauter, Vijay P. S. Rawat, Mirco Glitscher, Eberhard Hildt, Daniel Tews, Zachary Hunter, Jan Muench, Christian Buske
Summary: Waldenstrom's Macroglobulinemia is a B-cell lymphoma with aggressive disease in patients with CXCR4 mutations. A natural peptide called EPIX4 and its derivatives have shown to impair lymphoma cell growth, indicating potential novel therapies in Waldenstrom's Macroglobulinemia.
Article
Chemistry, Medicinal
Raghuvir Haridas Gaonkar, Yannik Tim Schmidt, Rosalba Mansi, Yasser Almeida-Hernanadez, Elsa Sanchez-Garcia, Mirja Harms, Jan Muench, Melpomeni Fani
Summary: The peptide fragment of human serum albumin, EPI-X4, was investigated as a scaffold for CXCR4-targeted radiotheragnostics. Ligand-7 (JM#21 derivative) showed the best CXCR4-tumor targeting and low uptake in non-targeted organs. These findings support the feasibility of using EPI-X4-based radioligands for CXCR4 targeting with ligand-7 as a lead candidate for further optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
Davide Calebiro, Zsombor Koszegi, Yann Lanoiselee, Tamara Miljus, Shannon O'Brien
Summary: Recent research has revealed transient interactions between GPCRs and G proteins in living cells, resulting in short-lived signaling nanodomains that may confer rapidity and specificity to signal transduction. These findings could potentially offer new strategies for modulating GPCR function and pave the way for innovative drug development for common diseases like diabetes or heart failure.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Biology
Pandian Sokkar, Mirja Harms, Christina Stuerzel, Andrea Gilg, Goenuel Kizilsavas, Martina Raasholm, Nico Preising, Manfred Wagner, Frank Kirchhoff, Ludger Staendker, Gilbert Weidinger, Benjamin Mayer, Jan Muench, Elsa Sanchez-Garcia
Summary: The research identified the key interaction motifs of EPI-X4 with CXCR4, explaining its receptor antagonization. Subsequently, shortened derivatives of EPI-X4 with optimized receptor antagonizing properties were developed as new leads for CXCR4 inhibitors.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Woong-Hee Shin, Keiko Kumazawa, Kenichiro Imai, Takatsugu Hirokawa, Daisuke Kihara
Summary: The driving mechanisms of many biological functions in a cell involve physical interactions between proteins. Protein-protein interactions (PPIs) also play a significant role in disease development, making them promising therapeutic targets in the pharmaceutical industry. This study introduces a novel method called protein-protein interaction-Surfer, which uses a three-dimensional Zernike descriptor (3DZD) to compare and quantify the similarity of local surface regions of PPIs. The performance of protein-protein interaction-Surfer was evaluated using datasets of PPIs, demonstrating its ability to identify similar potential drug binding regions without sequence and structure similarity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemical Research Methods
Xin Luo, Liwei Wang, Pengwei Hu, Lun Hu
Summary: This paper proposes a novel protein-protein interaction (PPI) prediction algorithm (PASNVGA) that combines sequence and network information to improve prediction accuracy. The algorithm utilizes principal component analysis to extract protein features and designs a scoring function to measure higher-order connectivity. By training a variational graph autoencoder model to learn integrated protein embeddings, the prediction task is completed using a feedforward neural network.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Takatsugu Kosugi, Masahito Ohue
Summary: The study developed a quantitative estimation index QEPPI specifically for early screening of compounds targeting protein-protein interactions, which showed better performance compared to the commonly used method QED.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Thi Ngan Dong, Graham Brogden, Gisa Gerold, Megha Khosla
Summary: The study developed a multitask transfer learning approach using large-scale protein sequence information and interaction patterns in the human interactome to address the issue of small training datasets. Experimental results demonstrated that the model achieved competitive results in virus-human and bacteria-human protein-protein interaction prediction tasks.
BMC BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ya Zhuo, Valeria L. Robleto, Adriano Marchese
Summary: beta-arrestins are versatile adaptor proteins that regulate various aspects of G protein-coupled receptor signaling. By using APEX-based proximity labeling, potential novel beta-arrestin interacting partners were discovered. Our study demonstrates that beta arr1-APEX can interact with known interacting proteins and label known beta arr1-interacting partners upon agonist stimulation. This study highlights the value of beta arr1-APEX-based proximity labeling in identifying novel players involved in GPCR signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Takatsugu Kosugi, Masahito Ohue
Summary: Over 930,000 protein-protein interactions (PPIs) have been identified, but targeting PPIs with conventional small molecules is challenging. A newly developed cyclic peptide complex offset, combined with AlphaFold2, can accurately predict the structure of target protein-cyclic peptide complexes and enable the design of putative cyclic peptide sequences targeting PPI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Pankaj Singh Dholaniya, Samreen Rizvi
Summary: Understanding protein-protein interactions is crucial for investigating the biological role of proteins. This study evaluates the efficacy of various sequence-based descriptors in predicting PPIs, with the results showing that the conjoint-triad descriptors performed the best.
CURRENT BIOINFORMATICS
(2021)
Article
Chemistry, Medicinal
Daniel Marx, Mohamed Wessam Alnouri, Sophie Clemens, Robin Gedschold, Yvonne Riedel, Ghazl Al Hamwi, Thanigaimalai Pillaiyar, Jorg Hockemeyer, Vigneshwaran Namasivayam, Christa E. Mueller
Summary: This study discovered a xanthine derivative that activates the main variant of MRGPRX4, and optimization resulted in analogs with high potency and metabolic stability. These compounds are promising tool compounds for exploring the potential of MRGPRX4 as a future drug target.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Jyrki P. Kukkonen
Summary: Recent data indicates cooperative effects between identical orthosteric binding sites in a G-protein-coupled receptor dimer. A mathematical model was created to test this concept, showing that even a neutral receptor ligand can allosterically affect agonist binding through the orthosteric binding site.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Alex D. Batista, Soumya Rajpal, Benedikt Keitel, Sandra Dietl, Beatriz Fresco-Cala, Mehmet Dinc, Rudiger Gross, Harald Sobek, Jan Munch, Boris Mizaikoff
Summary: This study developed epitope-imprinted polymers for selective binding of SARS-CoV-2, demonstrating high selectivity and potential applications in chem/biosensing and antiviral delivery.
ADVANCED MATERIALS INTERFACES
(2022)
Article
Multidisciplinary Sciences
Richard Kosinski, Joel Mieres Perez, Elisa-C Schoeneweiss, Yasser B. Ruiz-Blanco, Irene Ponzo, Kenny Bravo-Rodriguez, Michael Erkelenz, Sebastian Schluecker, Guido Uhlenbrock, Elsa Sanchez-Garcia, Barbara Sacca
Summary: In this study, thrombin is encaged into DNA origami cavities with different electrostatic features. The reaction rate is found to be affected by DNA/substrate electrostatic interactions, offering a new approach to regulate allosteric processes.
Article
Medicine, General & Internal
Ruediger Gross, Michelle Zanoni, Alina Seidel, Carina Conzelmann, Andrea Gilg, Daniela Krnavek, Suemeyye Erdemci-Evin, Benjamin Mayer, Markus Hoffmann, Stefan Poehlmann, Weimin Liu, Beatrice H. Hahn, Alexandra Beil, Joris Kroschel, Bernd Jahrsdoerfer, Hubert Schrezenmeier, Frank Kirchhoff, Jan Muench, Janis A. Mueller
Summary: According to a study on a cohort of individuals who received heterologous ChAdOx1 nCoV-19 BNT162b2 vaccination, the regimen induced potent humoral and cellular immune responses, with strong neutralization of the most prevalent SARS-CoV-2 variants. The results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern.
Article
Biochemical Research Methods
Mirja Harms, Rikke Fabech Hansson, Sheiliza Carmali, Yasser Almeida-Hernandez, Elsa Sanchez-Garcia, Jan Muench, Alexander N. Zelikin
Summary: This study focuses on the development of stabilized analogues of EPI-X4, an endogenous peptide antagonist of CXCR4. The Y-shaped conjugates were found to be more potent than the parent peptide and more stable in human plasma, showing promise for translational studies.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Virology
Lukas Wettstein, Patrick Immenschuh, Tatjana Weil, Carina Conzelmann, Yasser Almeida-Hernandez, Markus Hoffmann, Amy Kempf, Inga Nehlmeier, Rishikesh Lotke, Moritz Petersen, Steffen Stenger, Frank Kirchhoff, Daniel Sauter, Stefan Poehlmann, Elsa Sanchez-Garcia, Jan Muench
Summary: Host cell protease TMPRSS2 plays a critical role in the tropism and pathogenesis of SARS-CoV-2, and antithrombin (AT) is identified as a broad-spectrum inhibitor of coronavirus infection by blocking TMPRSS2 activity. AT can inhibit the entry of various coronaviruses, including SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2, and the Omicron variant, as well as suppress lung cell infection with genuine SARS-CoV-2. Activation of AT by anticoagulants enhances its activity against TMPRSS2 and SARS-CoV-2, suggesting the potential of repurposing AT for COVID-19 treatment.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Infectious Diseases
Yasser B. B. Ruiz-Blanco, Guillermin Agueero-Chapin, Sandra Romero-Molina, Agostinho Antunes, Lia-Raluca Olari, Barbara Spellerberg, Jan Muench, Elsa Sanchez-Garcia
Summary: The problem of multi-drug resistance in bacteria is a major global health issue. Peptides, which have binding specificity and low side effects, are seen as promising candidates for the development of new antibiotics. However, there is a lack of tools that can consistently predict the antibacterial activity of peptides. In this study, a new tool called ABP-Finder was introduced, which can identify antibacterial peptides and estimate the susceptibility of bacteria to their action. The tool ranks highly in terms of precision and has been successfully applied to screen a large peptide library and identify an antibacterial peptide.
Article
Biochemistry & Molecular Biology
Armando Rodriguez, Ernesto M. Martell-Huguet, Melaine Gonzalez-Garcia, Daniel Alpizar-Pedraza, Annia Alba, Antonio A. Vazquez, Mark Grieshober, Barbara Spellerberg, Steffen Stenger, Jan Muench, Ann-Kathrin Kissmann, Frank Rosenau, Ludger A. Wessjohann, Sebastian Wiese, Ludger Staendker, Anselmo J. Otero-Gonzalez
Summary: In this report, three novel antimicrobial peptides were identified from the marine mollusk Nerita versicolor. These peptides showed activity against Pseudomonas aeruginosa and exhibited antibiofilm action against Candida albicans. However, they were ineffective against other bacteria and fungi. The results suggest that these N. versicolor-derived peptides could be developed into antibiotic alternatives against bacterial and fungal infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Raghuvir Haridas Gaonkar, Yannik Tim Schmidt, Rosalba Mansi, Yasser Almeida-Hernanadez, Elsa Sanchez-Garcia, Mirja Harms, Jan Muench, Melpomeni Fani
Summary: The peptide fragment of human serum albumin, EPI-X4, was investigated as a scaffold for CXCR4-targeted radiotheragnostics. Ligand-7 (JM#21 derivative) showed the best CXCR4-tumor targeting and low uptake in non-targeted organs. These findings support the feasibility of using EPI-X4-based radioligands for CXCR4 targeting with ligand-7 as a lead candidate for further optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Dominik Schauenburg, Fabian Zech, Astrid Johanna Heck, Pascal von Maltitz, Mirja Harms, Siska Fuehrer, Nico Alleva, Jan Muench, Seah Ling Kuan, Frank Kirchhoff, Tanja Weil
Summary: Viral infections are a major threat to human health and require effective antiviral strategies. Antiviral peptides have emerged as a promising therapeutic approach due to their unique properties and mechanisms of action. In this study, we developed a chemical strategy to assemble a heterodimeric peptide conjugate on a protein-based nanoplatform, combining two optimized peptides that inhibit HIV-1 by distinct mechanisms. The constructed peptide showed increased activity against different variants of HIV-1, demonstrating the potential of assembling peptides with different modes of action on nanoplatforms to enhance antiviral activity.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Thomas Heerde, Desiree Schuetz, Yu-Jie Lin, Jan Muench, Matthias Schmidt, Marcus Faendrich
Summary: This study presents the Cryo-EM structure of a biotechnologically engineered peptide fibril called PNF-18, which enhances retroviral infectivity. It is found that these peptide fibrils undergo time-dependent morphological maturation and exhibit polymorphic amyloid structures. The structural data provide insights into the molecular basis of peptide nanofibrils as retroviral transduction enhancers.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mirja Harms, Nikaia Smith, Mingyu Han, Ruediger Gross, Pascal von Maltitz, Christina Stuerzel, Yasser B. Ruiz-Blanco, Yasser Almeida-Hernandez, Armando Rodriguez-Alfonso, Dominique Cathelin, Birgit Caspar, Bouceba Tahar, Sophie Sayettat, Nassima Bekaddour, Kanika Vanshylla, Franziska Kleipass, Sebastian Wiese, Ludger Staendker, Florian Klein, Bernard Lagane, Arnaud Boonen, Dominique Schols, Serge Benichou, Elsa Sanchez-Garcia, Jean-Philippe Herbeuval, Jan Muench
Summary: Seminal fluid-derived spermine selectively inhibits X4-HIV-1 infection, suggesting its role in limiting sexual transmission of this virus.
Article
Biology
Melanie Engler, Dan Albers, Pascal Von Maltitz, Ruediger Gross, Jan Muench, Ion Cristian Cirstea
Summary: SARS-CoV-2 binds to ACE2 to enter host cells, but other cell membrane receptors may also serve as virus-binding partners. This study reveals that EGFR is not only a spike protein binder, but also activated during SARS-CoV-2 infection. Inhibiting EGFR-MAPK activation reduces SARS-CoV-2 infection.
LIFE SCIENCE ALLIANCE
(2023)
Article
Materials Science, Biomaterials
Kuebra Kaygisiz, Arghya Dutta, Lena Rauch-Wirth, Christopher V. Synatschke, Jan Muench, Tristan Bereau, Tanja Weil
Summary: Amyloid-like nanofibers from self-assembling peptides have potential for therapeutic viral gene transfer. A machine learning approach was used to predict de novo sequences for viral infectivity enhancement, leading to the discovery of short but active peptides. This strategy is time- and cost-efficient for expanding the chemical space of self-assembling peptides.
BIOMATERIALS SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Christoph Karsten Jung, Jan Muench, Timo Jacob
Summary: This study elucidates the interaction mechanism between EPI-X4 and CXCR4 through a simulation approach. Two pivotal requirements for the interaction were predicted, providing new insights for therapeutic development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Michal Novotny, Matus Dubecky, Frantisek Karlicky
Summary: This paper investigates the accuracy of different DFT-based computational approaches in calculating the equilibrium lattice constants and exfoliation energy of hexagonal boron nitride (h-BN). The results are compared with experiments and reference QMC calculations to evaluate the accuracy of these computational methods.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)
Article
Chemistry, Multidisciplinary
Luigi Crisci, Federico Coppola, Alessio Petrone, Nadia Rega
Summary: The charge transfer dynamics in asymmetrically substituted indenotetracene molecules upon photo-excitation were investigated using real-time time-dependent density functional theory simulations. The study found that the electron-donating character of the substituents affects the overall electronic energy spacing and ultrafast charge transfer dynamics.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)
Article
Chemistry, Multidisciplinary
Vasilii Korotenko, Hendrik Zipse
Summary: The stability of various radicals and molecules has been studied using different theoretical methods, and good correlations between theoretical calculations and experimental results have been found. The effects of hydrogen bonding interactions on the stability of oxygen-centered radicals have also been investigated.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)
Article
Chemistry, Multidisciplinary
Oleg Egorov, Michael Rey, Dominika Viglaska, Andrei V. Nikitin
Summary: In this work, the rovibrational energy levels of four isotopologues of methylene were calculated using a new accurate ab initio potential energy surface. The accuracy of the calculations was improved by considering scalar relativistic effects, DBOC, and high-order electronic correlations. For the first time, all available experimental rovibrational transitions were reproduced with high accuracy, without any empirical corrections.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)