Article
Biochemistry & Molecular Biology
Chunlai Cao, Suzhen Wei, Xukun Xu, Suqin Song, Yongjie Lai, Jing Li
Summary: Dulaglutide is a safe and effective medication for type 2 diabetes, but N-terminal truncations pose a challenge. Signal peptide optimization, specifically using KASP, significantly improves the N-terminal integrity and productivity of GLP-1-Fc.
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Anil Kumar Marapaka, Priyanka Sankoju, Guozhen Zhang, Yongzheng Ding, Chunhua Ma, Vijaykumar Pillalamarri, Renu Sudhakar, Bharati Reddi, Puran Singh Sijwali, Yingjie Zhang, Anthony Addlagatta
Summary: This study describes the development of peptide-mimetic hydroxamates as antimalarial drugs, and compound 26 shows potent antimalarial activity and selectivity. The crystal structures provide insights into the molecular basis of its inhibitory activity and offer important clues for the design of selective and dual antimalarial agents.
CHINESE CHEMICAL LETTERS
(2022)
Article
Oncology
Ming Xiong, Chunyu Liu, Wencheng Li, Huiling Jiang, Wulin Long, Menghao Zhou, Chenlu Yang, Gallina Kazobinka, Yi Sun, Jun Zhao, Teng Hou
Summary: APA is a crucial regulatory mechanism in cancer development, and PABPN1 is an important gene in this process. In clear cell renal cell carcinoma, PABPN1 is upregulated and its expression is associated with clinical prognosis. PABPN1 promotes cancer progression by regulating genes like SGPL1 and CREG1.
Article
Biochemistry & Molecular Biology
Dimitris Matiadis, See-Ting Ng, Eric H-L Chen, Georgia Nigianni, Veroniki P. Vidali, Aleksander Canko, Rita P-Y Chen, Marina Sagnou
Summary: Ten hydroxylated monocarbonyl curcumin derivatives were designed, synthesized, and evaluated for their NEP upregulating potential, with compound 4 showing the highest activity. Derivatives bearing a cyclohexanone group exhibited higher activity enhancement compared to their acetone counterparts.
Article
Biochemistry & Molecular Biology
Jihae Shin, Qingbao Ding, Luyang Wang, Yange Cui, Erdene Baljinnyam, Aysegul Guvenek, Bin Tian
Summary: APA is an important aspect of gene expression program critical for defining cell identity. A method named CRISPRpas, which enhances proximal PAS usage, is developed to alter APA isoform abundance. The efficiency of CRISPRpas is influenced by various factors. The study demonstrates the modulation of APA for multiple endogenous genes and highlights the impact of CRISPRpas on gene expression.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jakob Rupert, Michele Monti, Elsa Zacco, Gian Gaetano Tartaglia
Summary: This study characterizes the physico-chemical properties of regions involved in amyloid aggregation using a computational approach, and investigates the influence of RNA on protein assembly. Experimental data shows that while the core region is hydrophobic and highly ordered, external regions exhibit a distinct tendency to interact with nucleic acids. RNA is found to accelerate aggregation, especially in a mutant truncated protein with a higher propensity for RNA interaction. The findings suggest that RNA sequestration might be a common phenomenon linked to protein aggregation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jianan Zhang, Yang Liu, Liwen Jiang, Tiantian Zhao, Guowan Su, Mouming Zhao
Summary: This research focused on elastin as the substrate and investigated the variations in peptide profiles and the production of key bioactive peptides. Through advanced analytical techniques, the study identified significant disparities in peptide concentrations across different elastin hydrolysates, hinting at varying levels of bioactive efficacy. The study identified 403 peptides within the elastin hydrolysates, with 18 peptides surpassing 5% in theoretical maximum content, signaling their crucial role in the hydrolysate's bioactivity.
Article
Pharmacology & Pharmacy
Roser Segovia, Mireia Diaz-Lobo, Yolanda Cajal, Marta Vilaseca, Francesc Rabanal
Summary: The efficient preparation of bioactive peptides requires reliable chemical methodologies and suitable analytical techniques. We describe a novel acidolytic method for the synthesis of cyclic and linear peptides. This method effectively removes protecting groups and cleaves peptides directly attached to resins without the need for mild labile linkers. The method was successfully used to synthesize antimicrobial peptides and electrospray mass spectrometry was effective for characterizing the composition of the peptides.
Review
Biochemistry & Molecular Biology
Janusz M. Gebicki, Thomas Nauser
Summary: Ionizing radiations cause chemical damage to proteins, commonly mediated by hydroxyl free radicals generated from water. Protein damage is significant in biological systems, as proteins are the main targets of radiation-generated radicals. Polyphenols and other compounds have the potential to repair protein radicals and prevent the formation of new reactive species.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jiaqiang Zhu, Wei Huang, Jing Zhao, Loc Huynh, Derek J. Taylor, Michael E. Harris
Summary: This study reveals the conformational changes during the recognition process of bacterial RNase P using high-throughput enzymology and cryoEM. The specific pairing of precursor tRNA inhibits the formation of the catalytic conformation. Comparisons of different precursor tRNA structures show that RNase P primarily uses stacking interactions and shape complementarity to accommodate alternative sequences. The study uncovers the active site interactions and conformational changes of RNase P, laying the foundation for understanding the link between binding interactions and catalysis.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Stephen A. Peter, Jessica S. Isaac, Franz Narberhaus, Julia E. Weigand
Summary: Proteome integrity is crucial for cellular homeostasis and adaptation to stress conditions like hypoxia, with alternative splicing being a mechanism for rapid adaptation. The isoE degron, generated under hypoxia, represents a universal protein degradation signal functional in mammalian cells, yeast, and bacteria. The conserved (F/W)xxW motif is essential for efficient protein decay mediated by the proteasome in eukaryotes and Lon protease in bacteria.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Meenakshi Sudhakaran, Tatiana Garcia Navarrete, Katherine Mejia-Guerra, Eric Mukundi, Timothy D. Eubank, Erich Grotewold, Daniel Arango, Andrea I. Doseff
Summary: Apigenin has been found to reprogram the transcriptome of triple-negative breast cancer (TNBC), inducing apoptosis and inhibiting tumor growth, offering new options for TNBC treatments.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Physical
Ziyi Wang, Zhongxing Zhao, Zeyue Yang, Guoqiang Li, Peng Zheng
Summary: Lead is a toxic metal that is harmful to human beings due to its long history and wide use in human society. It exerts toxicity through its interaction with proteins, particularly by targeting thiol-rich proteins and forming stable Pb-S bonds. A study was conducted using a de novo designed protein alpha 3DIV as a model protein to investigate Pb-S bonds. Atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) was used to detect specific Pb-S bond rupture signals, revealing the formation of a triangular pyramidal PbS3 site in alpha 3DIV and the pH-dependent weakening of Pb-S bond strength.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Jingwen Song, Syed Nabeel-Shah, Shuye Pu, Hyunmin Lee, Ulrich Braunschweig, Zuyao Ni, Nujhat Ahmed, Edyta Marcon, Guoqing Zhong, Debashish Ray, Kevin C. H. Ha, Xinghua Guo, Zhaolei Zhang, Timothy R. Hughes, Benjamin J. Blencowe, Jack F. Greenblatt
Summary: Alternative polyadenylation (APA) enhances gene regulatory potential by increasing the diversity of mRNA transcripts. A study found that the transcription factor Sp1 binds RNA and is a common repressor of distal poly(A) site usage. Sp1 inhibits cleavage at distal sites by interacting with the subunits of the core cleavage and polyadenylation (CPA) machinery.
Article
Chemistry, Physical
Ziyi Wang, Zhongxing Zhao, Zeyue Yang, Guoqiang Li, Peng Zheng
Summary: Lead is a toxic metal widely used in human society, but its interaction with proteins and formation of Pb-S bonds can cause toxicity. In this study, we used a de novo designed protein alpha 3DIV as a model protein to study Pb-S bonds. By detecting specific Pb-S bond rupture signals using atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS), we confirmed the formation of a triangular pyramidal PbS3 site in alpha 3DIV, including the previously undetected Pb-S(Cys67) bond. We also revealed and quantified the pH-dependent weakening of Pb-S bond strength, resulting in the dissociation of the PbS3 site at pH 4.5.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Alexandra De Zutter, Luna Dillemans, Nele Berghmans, Sam Noppen, Helena Crijns, Paulien Verscheure, Janne Verhaegen, Erik Martens, Lotte Vanbrabant, Noemie Portner, Dominique Schols, Paul Proost, Sofie Struyf
Summary: Glycosaminoglycans/proteoglycans (GAGs/PGs) play a crucial role in regulating tumor progression and can be potential targets for anti-cancer therapy. A D-amino acid version of CXCL9(74-103), called D-CXCL9(74-103), showed anti-angiogenic properties and inhibited endothelial spheroid sprouting and vessel formation. D-CXCL9(74-103) also exhibited anti-tumoral activity against heparan sulfate high B16-BL6 melanoma cells but had no effect on chondroitin sulfate high HCT116 colon carcinoma cells. These findings highlight the importance of tumor-associated GAGs in adhesion and metastasis and suggest the potential of D-CXCL9(74-103) as a therapeutic agent for heparan sulfate high tumors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Sarah Thompson, Chong Yun Pang, Krishna Mohan Sepuru, Seppe Cambier, Thomas P. Hellyer, Jonathan Scott, A. John Simpson, Paul Proost, John A. Kirby, Krishna Rajarathnam, Neil S. Sheerin, Simi Ali
Summary: Chemokine CXCL8 plays a crucial role in human immune response by mediating neutrophil migration and activation at sites of infection and injury. This study demonstrates that peroxynitrite can nitrate CXCL8, leading to impaired neutrophil migration and activation. The nitrated chemokine showed reduced ability to induce neutrophil migration in vitro and failed to promote leukocyte recruitment in vivo due to impaired receptor signaling and binding to glycosaminoglycans. The presence of nitrated CXCL8 was detected in bronchoalveolar lavage samples from patients with pneumonia, providing the first direct evidence of chemokine nitration in human pathophysiology.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lisa Verhallen, Jarkko J. J. Lackman, Rikke Wendt, Martin Gustavsson, Zhang Yang, Yoshiki Narimatsu, Daniel M. M. Sorensen, Kato Mac Lafferty, Mieke Gouwy, Pedro E. E. Marques, Gertrud M. M. Hjorto, Mette M. M. Rosenkilde, Paul Proost, Christoffer K. K. Goth
Summary: Chemokine ligands and receptors play a role in regulating leukocyte migration. This study examined the post-translational modifications of chemokine receptors and their impact on ligand binding and signaling. The results indicated that O-glycosylation and tyrosine sulfation affect the recognition and signaling of chemokines with the receptor CCR5. The enzymes GalNAc-T1 and GalNAc-T11 were identified as being involved in the O-glycosylation process of chemokine receptors.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Eva Ganseman, Mieke Gouwy, Dominique M. A. Bullens, Christine Breynaert, Rik Schrijvers, Paul Proost
Summary: A significant proportion of adult-onset asthma is caused by occupational exposure to various agents. Insect allergies can occur in several professions, with respiratory symptoms such as asthma being the most common. The recent approval of insects for human consumption by the European Union may increase the risk of occupational insect allergies. This review highlights the need for better diagnostics and primary prevention measures to protect workers in the developing insect industry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Karen Yu, Luna Dillemans, Mieke Gouwy, Helena Bessa, Mieke Metzemaekers, Erik Martens, Patrick Matthys, Xavier Bossuyt, Patrick Verschueren, Carine Wouters, Lien De Somer, Paul Proost
Summary: In this study, a fluorescent in vitro assay was improved to characterize endogenous PAD activity in complex samples. The results showed similar levels of PAD activity in synovial fluids of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) patients, while citrullination was limited in joints of patients with gout or Lyme's disease. Interestingly, a higher level of extracellular citrullination was only found in blood of anti-CCP-positive RA patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Chemistry, Medicinal
Mieke Metzemaekers, Bert Malengier-Devlies, Mieke Gouwy, Lien De Somer, Fernando de Queiroz Cunha, Ghislain Opdenakker, Paul Proost
Summary: Neutrophils are powerful effector cells that play crucial roles in fighting pathogens and modulating immune responses. Recent evidence suggests that these cells are more versatile and heterogeneous than previously thought, and are involved in various diseases including cancer and autoimmune disorders. This review discusses the kinetics of neutrophils and their activation products, as well as their multifaceted functions in health and disease, focusing on studies using primary human cells.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Rheumatology
Bernard Grillet, Rafaela Vaz Sousa Pereira, Jo Van Damme, Ahmed Abu El-Asrar, Paul Proost, Ghislain Opdenakker
Summary: Proteolysis of the extracellular matrix is an irreversible post-translational modification in arthropathies like osteoarthritis and rheumatoid arthritis due to increased levels of matrix remodelling enzymes such as matrix metalloproteinases (MMPs). MMPs destroy proteoglycans, collagens, and other ECM molecules and also control joint remodelling indirectly through cell-surface receptors and cytokines. Understanding the regulation and activities of MMPs can help develop better diagnostics and therapies for joint diseases. MMPs play a significant role in irreversible joint remodelling in rheumatoid arthritis and osteoarthritis, making them important targets for precision medicine and diagnosis.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Letter
Medicine, General & Internal
Ellen De Langhe, Sien Van Loo, Bert Malengier-Devlies, Mieke Metzemaekers, Frederik Staels, Jessica Vandenhaute, Nathalie Berghen, Raf Sciot, Anniek Corveleyn, Olga Tsuiko, Mieke Gouwy, Jan Lenaerts, Patrick Verschueren, Carine H. Wouters, Paul Proost, Patrick Matthys, Eric Legius, Rik Schrijvers
Summary: The article reports a case of adult-onset inflammatory disease. It is revealed that two somatic genetic events are responsible for the disease and its onset in adulthood.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Seppe Cambier, Fabio Beretta, Noemie Portner, Mieke Metzemaekers, Ana Carolina de Carvalho, Erik Martens, Janne Kaes, Celine Aelbrecht, Cato Jacobs, Pierre Van Mol, Els Wauters, Philippe Meersseman, Greet Hermans, Rafael Elias Marques, Bart Vanaudenaerde, Robin Vos, Joost Wauters, Mieke Gouwy, Paul Proost
Summary: CXCL12, which is present in the lungs and circulation of COVID-19 patients, undergoes rapid proteolytic processing and degradation. The proteolysis is mainly mediated by neutrophil elastase in COVID-19 BAL fluids with high proteolytic activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Allergy
Toon Ieven, Lieve Coorevits, Martijn Vandebotermet, Sebastiaan Tuyls, Helene Vanneste, Lisa Santy, Dries Wets, Paul Proost, Glynis Frans, David Devolder, Christine Breynaert, Dominique M. A. Bullens, Rik Schrijvers
Summary: This study evaluated the tolerance of PEGylated lipid nanoparticle vaccine (BNT162b2) in patients with PEG and/or PS80 allergy and explored the mechanism of reactivity. The results showed that all PEG and/or PS80 allergic patients can safely receive SARS-CoV-2 vaccines.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Meeting Abstract
Endocrinology & Metabolism
Shauni Loopmans, Steve Stegen, Katerina Rohlenova, Ingrid Stockmans, Karen Moermans, Peter Carmeliet, Geert Carmeliet
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Bruna M. Silva, Giovanni F. Gomes, Flavio P. Veras, Seppe Cambier, Gabriel V. L. Silva, Andreza U. Quadros, Diego B. Caetite, Daniele C. Nascimento, Camilla M. Silva, Juliana C. Silva, Samara Damasceno, Ayda H. Schneider, Fabio Beretta, Sabrina S. Batah, Icaro M. S. Castro, Isadora M. Paiva, Tamara Rodrigues, Ana Salina, Ronaldo Martins, Guilherme C. M. Cebinelli, Naira L. Bibo, Daniel M. Jorge, Helder I. Nakaya, Dario S. Zamboni, Luiz O. Leiria, Alexandre T. Fabro, Jose C. Alves-Filho, Eurico Arruda, Paulo Louzada-Junior, Rene D. Oliveira, Larissa D. Cunha, Pierre Van Mol, Lore Vanderbeke, Simon Feys, Els Wauters, Laura Brandolini, Andrea Aramini, Fernando Q. Cunha, Joerg Koehl, Marcello Allegretti, Diether Lambrechts, Joost Wauters, Paul Proost, Thiago M. Cunha
Summary: Activation of the C5a/C5aR1 pathway in COVID-19 patients can worsen the disease and lead to cytokine storm syndrome, organ dysfunction, and death. Inhibiting C5aR1 signaling can improve lung immunopathology, suggesting that C5aR1 antagonists may be useful for COVID-19 treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Immunology
Seppe Cambier, Mieke Gouwy, Paul Proost
Summary: Chemokines play a crucial role in regulating leukocyte migration and activation in the immune system. CXCL8 is a potent chemokine that attracts neutrophils and is important in the response to infection and tissue injury. Its activity is dependent on interactions with specific chemokine receptors and glycosaminoglycans. Understanding the structure and regulation of CXCL8 is important for therapeutic development and managing inflammatory diseases and cancer.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Luna Dillemans, Youri Bekhuis, Albrecht Betrains, Karen Yu, Maarten van Hemelen, Noemie Portner, Lien De Somer, Patrick Matthys, Jeroen Breckpot, Thomas Tousseyn, Marijke Peetermans, Paul Proost, Carine Wouters, Steven Vanderschueren
Summary: We report a fatal case of a 20-year-old woman with refractory adult-onset Still's disease accompanied by fulminant macrophage activation syndrome and atypical hemolytic uremic syndrome. This case highlights the importance of prompt genetic assessment of complement-encoding alleles, in addition to HLH-related genes, in patients with severe adult-onset Still's disease with recurrent macrophage activation syndrome and features of thrombotic microangiopathy.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Olav Larsen, Sara Schuermans, Anna Walser, Stavroula Louka, Ida Aaberg Lillethorup, Jon Vabeno, Katrine Qvortrup, Paul Proost, Mette M. Rosenkilde
Summary: This study investigates the signaling capacity of peptides related to inflammatory chemokines. The peptides showed weak potency but retained their signaling on CCR1, while none of the peptides generated a signal on CCR5. However, a tetrapeptide derived from CCL3 acted as a positive modulator on CCR5.