Article
Biochemistry & Molecular Biology
Carlos Fernandez-Pereira, Maria Aranzazu Penedo, Tania Rivera-Baltanas, Rafael Fernandez-Martinez, Saida Ortolano, Jose Manuel Olivares, Roberto Carlos Agis-Balboa
Summary: This study aimed to evaluate whether the alterations in insulin-like growth factor 2 (IGF-2) and IGF binding protein 7 (IGFBP-7) in schizophrenia patients are related to the psychiatric disorder itself or are a result of antipsychotic treatment. The results showed that drug-naive first episode patients had lower levels of IGF-2 compared to controls, but no significant change in IGFBP-7 levels. However, both IGF-2 and IGFBP-7 significantly increased after atypical antipsychotic treatment in these patients. Chronic patients, on the other hand, had higher levels of both proteins compared to controls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Derek LeRoith, Jeff M. P. Holly, Briony E. Forbes
Summary: The IGF family of ligands, receptors, and binding proteins play critical roles in normal human physiology and disease states. IGF-I regulates cellular growth, differentiation, and survival to control overall body growth, while IGF-II has important effects prenatally and in tissue-specific roles in adults.
MOLECULAR METABOLISM
(2021)
Review
Endocrinology & Metabolism
Mengyang Li
Summary: The GH/IGF system plays a role in growth regulation in the body. By studying the basal chordate amphioxus, it was discovered that most members of the GH/IGF system are present in amphioxus, providing strong evidence for the origin of this system in amphioxus.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Charmaine J. Green, Miriam Span, Monique H. Rayhanna, Marisa Perera, Margot L. Day
Summary: The viability of embryos cultured in vitro is poor compared to those that develop in vivo. This study investigated the role of autocrine and exogenous IGFBP3 in mouse preimplantation embryos. Addition of exogenous IGFBP3 to embryo culture media increased the rate of development, and the effect was mediated by IGF1 and EGF receptors. Acute exposure to IGFBP3 activated the PI3-kinase/Akt pathway to promote cell proliferation and survival. Therefore, addition of IGFBP3 to IVF culture media should be considered.
Review
Biochemistry & Molecular Biology
Shiva Nasr, Athar Nakisa, Setareh Jandaghian, Monireh Kouhi, Erfan Sadeghi, Jaleh Varshosaz
Summary: This systematic review found that flavonoid supplements do not have a significant effect on IGF-1 and IGFBP-3. However, a high soy diet has beneficial effects on components of the IGF system, which may be useful in breast cancer.
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Fatemeh Meshkini, Nahid Ramezani-Jolfaie, Saman Sargazi, Cain C. T. Clark, Sepideh Soltani
Summary: A systematic review of the effects of lycopene on circulating IGF-1 and IGFBPs in adults found no consistent modifying effect of lycopene supplementation on IGF-1 and IGFBP levels. More research is needed to explore the effect of lycopene on the IGF-1 system.
PHYTOTHERAPY RESEARCH
(2022)
Article
Oncology
Huong Thuy Le, Ho Jin Lee, Jaebeom Cho, Hye-Young Min, Ji-Sun Lee, Su-Jae Lee, Ho-Young Lee
Summary: The study demonstrates the anti-metastatic effects of IGFBP-3 in inhibiting migration and invasion of NSCLC and HNSCC cells, as well as the development of metastasized tumors in vivo. Mechanistically, IGFBP-3 disrupts the protein stability of vimentin via direct binding, providing a molecular explanation for its IGF-independent anti-metastatic and anti-tumor activities.
Article
Cell & Tissue Engineering
Haijian Sun, Shuang Wang, Zheng Yang, Lijie Tian, Xiaoxia Li, Jie Zhou, Baoli Wang
Summary: In this study, the researchers found that CHRDL1 acts as an antagonist of BMPs by binding to them and blocking their interaction with BMP receptors. They revealed that CHRDL1 suppresses osteoblast differentiation while promoting adipocyte differentiation. Mechanistic exploration showed that CHRDL1 stabilizes IGFBP3 and differentially modulates AKT/mTORC1 signaling, thereby regulating the differentiation of osteoblasts and adipocytes.
Article
Agriculture, Dairy & Animal Science
Mengying Dou, Md. Abul Kalam Azad, Yating Cheng, Sujuan Ding, Yang Liu, Bo Song, Xiangfeng Kong
Summary: Animal growth after weaning is influenced by various factors, including breed, nutrition, growth hormones, physiological stage, and environment. This study investigated the insulin-like growth factor (IGF) system components in different pig breeds during weaning and found that expressions of IGF system components were affected by weaning stress and differed among the breeds.
Article
Medicine, General & Internal
Barbara Wlodarczyk, Lukasz Durko, Przemyslaw Wlodarczyk, Renata Talar-Wojnarowska, Ewa Malecka-Wojciesko
Summary: Differentiating between pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) poses a challenge. This study assessed the usability of IGF-1, IGFBP-2, and IGF-1/IGFBP-2 ratio in differentiating PDAC and CP. The results indicate that CA 19-9 demonstrates high potential as a marker for PDAC and CP differentiation.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Rikke Hjortebjerg, Maja R. Kristiansen, Ivan Brandslund, Dorte Aa. Olsen, Jacob V. Stidsen, Jens S. Nielsen, Jan Frystyk
Summary: In individuals with type 2 diabetes, high levels of IGFBP-2 are associated with low glucose and insulin secretion, are unaffected by metformin treatment, and are associated with the risk of prior comorbidity and mortality.
DIABETES RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Endocrinology & Metabolism
Chloe Rauzier, Dominic J. Chartrand, Natalie Almeras, Isabelle Lemieux, Eric Larose, Patrick Mathieu, Philippe Pibarot, Benoit Lamarche, Caroline Rheaume, Paul Poirier, Jean-Pierre Despres, Frederic Picard
Summary: This study found that low levels of IGFBP-2 are associated with fat accumulation and metabolic alterations in individuals with obesity. However, it remains unclear whether IGFBP-2 affects energy metabolism in the early stages of these disorders.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Medicine, General & Internal
Xiaohui Wang, Jia Li, Wei Zhang, Feng Wang, Yunzi Wu, Yulin Guo, Dong Wang, Xinfeng Yu, Ang Li, Fei Li, Yibin Xie
Summary: This study reveals that tumor-derived IGFBP-3 plays a critical role in cancer-associated cachexia by causing lipid loss in mature adipocytes. IGFBP-3 antagonizes insulin/IGF-like signaling and impairs the balance between lipolysis and lipogenesis. The findings suggest that tumor-derived IGFBP-3 may serve as a biomarker for the diagnosis of cachexia in cancer patients.
CHINESE MEDICAL JOURNAL
(2023)
Article
Nutrition & Dietetics
Dong Hoon Lee, Fred K. Tabung, Edward L. Giovannucci
Summary: This study found that higher intake of animal protein is associated with higher levels of IGF-1 and lower levels of IGFBP-1 and IGFBP-2, while higher intake of plant protein is associated with higher levels of IGF-1 and IGFBP-1. These associations are more significant in participants with unhealthy lifestyle risk factors.
CLINICAL NUTRITION
(2022)
Review
Oncology
Jennifer A. Waters, Ixchel Urbano, Mikella Robinson, Carrie D. House
Summary: This review discusses the different roles of IGF signaling and IGFBP5 in disease, emphasizing the need to clarify the IGF-independent actions of IGFBP5, the impact of its subcellular localization, the differential activities of each subdomain, and the response to elements of the tumor microenvironment (TME). Recent advances addressing the role of IGFBP5 in resistance to cancer therapeutics are also discussed.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Anneliese S. Ashhurst, Arthur H. Tang, Pavla Fajtova, Michael C. Yoon, Anupriya Aggarwal, Max J. Bedding, Alexander Stoye, Laura Beretta, Dustin Pwee, Aleksandra Drelich, Danielle Skinner, Linfeng Li, Thomas D. Meek, James H. McKerrow, Vivian Hook, Chien-Te Tseng, Mark Larance, Stuart Turville, William H. Gerwick, Anthony J. O'Donoghue, Richard J. Payne
Summary: The study identifies cathepsin L as a key protease used by coronaviruses for cell entry and a potential drug target for antiviral treatment against SARS-CoV-2. The researchers discovered that gallinamide A and synthetic analogues are potent inhibitors of cathepsin L, showing promising antiviral activity against SARS-CoV-2. The combination with a TMPRSS2 inhibitor further enhances the antiviral effect.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Rahul S. Samant, Silvia Batista, Mark Larance, Bugra Ozer, Christopher I. Milton, Isabell Bludau, Estelle Wu, Laura Biggins, Simon Andrews, Alexia Hervieu, Harvey E. Johnston, Bissan Al-Lazikhani, Angus I. Lamond, Paul A. Clarke, Paul Workman
Summary: The molecular chaperone HSP90 plays a role in stabilizing client proteins involved in oncogenesis and malignant progression. Inhibitors of HSP90 have diverse effects on the proteome, but previous studies have mainly focused on total protein levels rather than protein complex alterations. This study used SEC-MS to characterize early changes in native protein complexes after treatment with the HSP90 inhibitor tanespimycin in colon adenocarcinoma cells. The study identified novel HSP90 inhibitor-modulated proteins and provides a resource for further research in HSP90 pharmacology. The data is available via ProteomeXchange (identifier: PXD033459).
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Hematology
Angelina J. Lay, Alexander Dupuy, Lejla Hagimola, Jessica Tieng, Mark Larance, Yunwei Zhang, Jean Yang, Yvonne Kong, Joyce Chiu, Emilia Gray, Zihao Qin, Diana Schmidt, Jessica Maclean, Benjamin Hofma, Marc Ellis, Maggie Kalev-Zylinska, Yair Argon, Shaun P. Jackson, Philip Hogg, Freda H. Passam
Summary: This study found that ERp5 plays a negative regulatory role in platelet ER stress response and highlights the importance of disulfide isomerases in platelet ER homeostasis. Furthermore, the study also revealed the close correlation between platelet ER stress and platelet secretion and thrombosis.
Article
Biochemical Research Methods
Poanna Tran, Hue N. T. Tran, Kirsten L. McMahon, Jennifer R. Deuis, Lotten Ragnarsson, Alexander Norman, Simon J. Sharpe, Richard J. Payne, Irina Vetter, Christina I. Schroeder
Summary: This study aimed to design new bivalent inhibitors of Na(V)1.7 by combining the pore blocking activity of conotoxins with the gating modifier activity of spider toxins. The potency and selectivity of the resulting bivalent toxins were evaluated by ligating a conotoxin to a spider toxin. The bivalent peptide Pro[LPATG(6)]Sx, resulting from the ligation of ProTx-II and SxIIIC, showed the best combination with conserved potency at hNa(V)1.7.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: N6-(((trimethylsilyl)-methoxy)carbonyl)-L-lysine (TMSK) and N6-trifluoroacetyl-L-lysine (TFAK) are non-canonical amino acids that can be incorporated into proteins via genetic encoding. A new aminoacyl-tRNA synthetase specific for N6-(((trimethylsilyl)methyl)-carbamoyl)-L-lysine (TMSNK) is described, which is chemically more stable than TMSK. The study demonstrates the use of these amino acids for site-specific NMR analysis of ligand binding to large proteins of limited stability and at low concentrations.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Hue N. T. Tran, Elena Budusan, Natalie J. Saez, Alexander Norman, Isaac J. Tucker, Glenn F. King, Richard J. Payne, Lachlan D. Rash, Irina Vetter, Christina I. Schroeder
Summary: Hi1a is a naturally occurring bivalent spider-venom peptide that shows promise for limiting ischemic damage. However, challenges in synthesizing and producing the peptide in large quantities have hindered progress in this area. Access to synthetic Hi1a is crucial for its development as a pharmacological tool and potential therapeutic.
Article
Multidisciplinary Sciences
Tara K. Bartolec, Xabier Vazquez-Campos, Alexander Norman, Clement Luong, Marcus Johnson, Richard J. Payne, Marc R. Wilkins, Joel P. Mackay, Jason K. K. Low
Summary: Significant advances in cryoelectron microscopy have expanded our ability to create structural models of proteins and protein complexes. Cross-linking mass spectrometry (XL-MS) is demonstrated to be a powerful tool for high-throughput experimental assessment of protein structures and interactions. The combination of XL-MS data with AlphaFold2 predictions offers opportunities to explore the structural proteome and interactome in depth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Organic
Arthur H. Tang, Richard J. Payne
Summary: Gallinamide A, a natural product produced by cyanobacteria, shows potent anti-parasitic activity by inhibiting essential cysteine protease enzymes. It has also been found to possess strong antiviral activity against SARS-CoV-2 by covalently inhibiting the host cysteine protease cathepsin L involved in viral entry. To conduct detailed pre-clinical studies on its potential as a COVID-19 antiviral, a more efficient synthetic route was developed to obtain significant quantities of this natural product. The second generation total synthesis of Gallinamide A described here delivered the compound in a yield of 32% on a 315 mg scale over 16 steps (9 steps in the longest linear sequence).
Article
Cell Biology
Dylan J. Harney, Michelle Cielesh, Georgia E. Roberts, Isabelle K. Vila, Barney Viengkhou, Markus J. Hofer, Nadine Laguette, Mark Larance
Summary: Intermittent fasting (IF) is an effective intervention for treating obesity, but its interaction with sex is still not fully understood. This study uses unbiased proteome analysis to identify diet-sex interactions and reveals sexual dimorphism in lipid and cholesterol metabolism, as well as unexpected differences in type I interferon signaling. The secretion of type I interferon is found to be essential for the IF response in females. Additionally, the study shows that sex hormone signaling can either suppress or enhance the interferon response to IF. The findings also indicate that the IF response varies with genotype and environment, highlighting the complex interaction between diet, sex, and the innate immune system.
Review
Chemistry, Multidisciplinary
Katriona Harrison, Angus S. Mackay, Lucas Kambanis, Joshua W. C. Maxwell, Richard J. Payne
Summary: The homochirality of biomolecules in nature has been crucial for the existence of life and has also provided opportunities for synthetic chemists to generate molecules with inverted chirality. Recent work on synthetic mirror-image proteins, using modern synthetic strategies, has led to their applications in protein crystallography, drug discovery, and the creation of mirror-image life.
NATURE REVIEWS CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Clara Bersi Motta Correa, Ana Carolina Kogawa, Marlus Chorilli, Herida Regina Nunes Salgado
Summary: Tyrosine sulfation is a post-translational modification that plays a crucial role in modulating the function of salivary proteins from blood feeding organisms. Utilizing synthetic chemistry, homogeneously sulfated peptides and proteins have been generated to study their structure and function. This research has provided valuable insights into the importance of tyrosine sulfate in enhancing anticoagulant activity.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Oliver H. Rathje, Lara Perryman, Richard J. Payne, Dieter W. Hamprecht
Summary: In this study, a novel approach called PROteolysis TArgeting Chimeras (PROTACs) was developed to effectively degrade MLKL and completely inhibit cell death. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further understand the role of MLKL within the necroptotic pathway.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Shankar Raj Devkota, Pramod Aryal, Rina Pokhrel, Wanting Jiao, Andrew Perry, Santosh Panjikar, Richard J. Payne, Matthew C. J. Wilce, Ram Prasad Bhusal, Martin J. Stone
Summary: This study focused on a type of chemokine-binding proteins called A3 evasins from tick saliva, which can bind with CC chemokines and inhibit their receptor activation. Structure-based modifications of A3 evasins can alter their chemokine selectivity, suggesting their potential applications in targeted anti-inflammatory therapy.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: TMSK, TMSNK, and TFAK are non-canonical amino acids that can be incorporated into proteins through genetic encoding. A new aminoacyl-tRNA synthetase specific for TMSNK is described, which is chemically more stable. Using the SARS-CoV-2 main protease (Mpro) as a model system, intense signals in the nuclear magnetic resonance (NMR) spectrum were observed for the trimethylsilyl and CF3 groups. The response of these groups to active-site ligands differed depending on their proximity to the active site, and the previously reported binding site of the ligand pelitinib was not confirmed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Cameron C. Hanna, Joshua W. C. Maxwell, Hendra S. Ismanto, Anneliese S. Ashhurst, Lukas M. Artner, Santosh Rudrawar, Warwick J. Britton, Sho Yamasaki, Richard J. Payne
Summary: The covalent fusion of immunostimulatory adjuvants to immunogenic antigens is a promising strategy for the development of effective synthetic vaccines for infectious diseases. This article describes the conjugation of a mycobacterial peptide antigen ESAT6 to a potent glycolipid adjuvant TDB targeting Mincle.
CHEMICAL COMMUNICATIONS
(2022)
