Review
Chemistry, Multidisciplinary
Xinjian Ji, Alexander L. Nielsen, Christian Heinis
Summary: Cyclic peptides are a class of molecules widely found in nature and used in drug development. Advances in synthesis and drug development have led to the creation of many cyclic peptide drugs. Cyclic peptides possess favorable properties that make them attractive for drug development. Currently, there are over 40 cyclic peptide drugs in use, and new technological advances suggest that this number could rapidly increase.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Pharmacology & Pharmacy
Vladislav I. Deigin, Elena A. Poluektova, Allan G. Beniashvili, Sergey A. Kozin, Yuri M. Poluektov
Summary: Peptides are low-molecular-weight substances that play important roles in various physiological functions. While synthesis of peptide drugs has been possible for over a century, there are still challenges in enhancing their stability, bioavailability, and cell membrane penetration. This article provides a brief overview of the history of peptide production and development in the biochemical industry, explores potential applications of peptide biopharmaceuticals, and discusses modern approaches for creating pharmaceuticals based on synthetic peptides and their analogs, with a focus on original peptide drugs developed by the Russian Federation.
Article
Chemistry, Analytical
Kai Zhang, Lei Zhou, Tingting Zhang, Zhenqiang Fan, Minhao Xie, Yuedi Ding, Hao Li
Summary: A biosensing method was developed to detect protein function under pathological conditions, showing oxidative stress-induced protein translocation and modification. Clinical samples confirmed the effectiveness of this method in studying the role of proteins in the progression of colorectal cancer.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Chemistry, Physical
Taiyu Liu, Lu Li, Cheng Cheng, Bingfang He, Tianyue Jiang
Summary: Protein/peptide-based nanoassemblies are widely used in drug delivery and vaccine development due to their well-defined architecture, accurate molecular weight, excellent biocompatibility and biodegradability, and easy-to-functionalization. Inspired by nature, self-assembling proteins/peptides have been explored and designed to generate nanoassemblies with unique structure and function. This review summarizes the recent advances in protein/peptide-based nanoassemblies, including protein nanocages, virus-like particles, self-assemblable natural proteins, and self-assemblable artificial peptides, and discusses the prospects and challenges for further development.
Review
Biochemistry & Molecular Biology
Uttpal Anand, Anustup Bandyopadhyay, Niraj Kumar Jha, Jose M. Perez de la Lastra, Abhijit Dey
Summary: Protein-protein interactions play a crucial role in drug development, but disrupting PPIs with small molecules is challenging. Peptides with both conformational rigidity and flexibility are able to target difficult binding interfaces. Over 80 peptide drugs have been approved for various diseases, including cancer and HIV infection. New strategies, such as peptide display libraries and integrated genomics, are being developed for peptide drug discovery.
Article
Engineering, Environmental
Jingyao Wang, Alexandria Niemoeller, Shekhar Viswanath
Summary: Solid phase peptide synthesis is an important technique for producing medicinal peptides, and optimizing reaction conditions using minimum screening experiments is crucial for peptide production and isolation.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Dazhi Feng, Lihua Liu, Yuqi Shi, Pian Du, Shengtao Xu, Zheying Zhu, Jinyi Xu, Hong Yao
Summary: Bicyclic peptides, with two loops within their structure, have emerged as powerful tools in the development of new peptide drugs due to their potential to bind to challenged drug targets with antibody-like affinity and selectivity. They also possess small molecule-like access to chemical synthesis, enabling large-scale synthesis and screening. This perspective provides an overview of the structure types, synthesis, and applications of bicyclic peptides in current drug development and discusses future challenges.
CHINESE CHEMICAL LETTERS
(2023)
Review
Pharmacology & Pharmacy
Xin Cai, Dexiu Wang, Rumin Zhang, Yanchun Chen, Jing Chen
Summary: GPCR dimers play important roles in regulating physiological and pathological functions, making them novel drug targets for various diseases. The formation and stability of GPCR dimers are closely associated with conformational changes in the transmembrane domain, which also affect their function. Therefore, the transmembrane domain is an emerging target for developing drugs that target GPCR dimerization.
DRUG DISCOVERY TODAY
(2023)
Review
Engineering, Biomedical
A. Zaghmi, J. Drouin-Ouellet, D. Brambilla, M. A. Gauthier
Summary: The presence of impermeable blood-brain barriers restricts access of protein therapeutics to the brain, making treating brain disorders a great challenge. Exploring new approaches to deliver proteins to the brain by circumventing physiological barriers is of great interest and importance.
Article
Neurosciences
Bin Lu, Chao-Gan Yan
Summary: Quality control is crucial in fMRI studies, as it helps to eliminate images without adequate quality. In this study, we used DPABI pipelines to preprocess an open-available dataset and illustrated the QC procedure. Results showed that 8.6% of participants were excluded and 5.8% were categorized as uncertain after the QC procedure. While automatic QC tools are needed in the big-data era, visually inspecting images is still essential.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Ciaran P. Seath, Antony J. Burton, Xuemeng Sun, Gihoon Lee, Ralph E. Kleiner, David W. C. MacMillan, Tom W. Muir
Summary: Interactions between biomolecules are important for cellular processes and can be disrupted by mutations or external factors, leading to changes in cellular physiology, which can have disease or therapeutic effects. Studying these interactions and their response to stimuli is crucial for drug development, leading to improvements in human health.
Article
Pharmacology & Pharmacy
Myung-Hee Chun, Ji Yeon Kim, Eun-Seok Park, Du Hyung Choi
Summary: This study optimized the formulation and process of bilayer tablets using the QbD approach, with d-optimal mixture design and response surface design. Multivariate analysis and PAT were used to analyze correlations and confirm material attributes, leading to the achievement of bioequivalence for the bilayer tablets.
Review
Chemistry, Medicinal
Robert Liebner, Sarah Altinoglu, Torsten Selzer
Summary: Biopharmaceuticals for human use present unique challenges in manufacturing, storage, shipment, and administration. There is a lack of regulatory guidance for phase appropriate process development studies for clinical supplies. This review proposes a phase appropriate testing approach for liquid protein formulations.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Engineering, Biomedical
Shixian Lv, Meilyn Sylvestre, Kefan Song, Suzie H. Pun
Summary: Melittin, the primary peptide component in bee venom, has anti-tumor activity but its practical application is hindered by hemolytic activity and instability. Use of D-amino acids in place of L-amino acids reduces immunogenicity of melittin, allowing for safer delivery and maintaining cytolytic potential. D-melittin micelles show cytotoxicity in a pH-dependent manner, inducing immunogenic cell death and demonstrating potential for cancer immunotherapy. The study presents a new strategy for systemic delivery of cytotoxic peptides in cancer treatment.
Article
Chemistry, Medicinal
Jingjing Zhang, Jimin Yuan, Zhijie Li, Chunjin Fu, Menglong Xu, Jing Yang, Xin Jiang, Boping Zhou, Xiufeng Ye, Chengchao Xu
Summary: Natural peptides, including plant cyclic peptides, have become a significant resource for therapeutic development, with the latter's potential largely unexplored. Plant cyclic peptides, known for their rigid structures and good bioavailability, are promising candidates for drug development. Utilizing genome information from various plants can aid in the rapid discovery of new cyclic peptides, leading to the exploration of more peptide drugs derived from plants.
MEDICINAL RESEARCH REVIEWS
(2021)
Review
Environmental Sciences
Sileshi Belew, Sultan Suleman, Evelien Wynendaele, Luc Duchateau, Bart De Spiegeleer
Summary: This study conducted an environmental risk assessment of the anthelmintic medicine albendazole in the eastern African region, revealing potential environmental risks of albendazole in surface water and soil in that region, calling for actions to mitigate these risks.
ENVIRONMENTAL POLLUTION
(2021)
Article
Chemistry, Medicinal
Ruyu Dai, Wei Zhang, Wending Tang, Evelien Wynendaele, Qizhi Zhu, Yannan Bin, Bart De Spiegeleer, Junfeng Xia
Summary: BBPpred is a computational method for predicting blood-brain barrier peptides that efficiently identifies informative features and shows promising performance on both training and independent test datasets.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Biochemistry & Molecular Biology
Christophe van de Wiele, Sezgin Ustmert, Bart De Spiegeleer, Pieter-Jan De Jonghe, Mike Sathekge, Maes Alex
Summary: Various potential PET-apoptosis imaging radiopharmaceuticals have been developed to assess the response to cancer treatment. Some of these radiopharmaceuticals showed enhanced uptake in xenografted tumors in mice, but to varying degrees. Two validated radioligands showed favorable characteristics in healthy individuals, but did not significantly affect bone marrow. Further research is needed to evaluate the clinical value of these radiopharmaceuticals for apoptosis imaging in cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Letter
Gastroenterology & Hepatology
Frederick Verbeke, Bart De Spiegeleer
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
(2021)
Article
Geriatrics & Gerontology
Anton De Spiegeleer, Jordi Van Migerode, Antoon Bronselaer, Evelien Wynendaele, Milan Peelman, Filip Vandaele, Geert Byttebier, Guy De Tre, Luc Belmans, Christophe Van de Wiele, Mike Sathekge, Diemer Van Dijck, Bo Saxberg, Myriam Alexander, David Fedson, Dirk Elewaut, Nele Van den Noortgate, Bart De Spiegeleer
Summary: This study suggests that the use of statins in nursing home residents can reduce all-cause mortality, indicating the potential geroprotector effect of statins in this population. More research is needed to further investigate this effect.
Article
Chemistry, Analytical
Frederick Verbeke, Kevin Van der Borght, Anton De Spiegeleer, Nathan Debunne, Yorick Janssens, Evelien Wynendaele, Bart De Spiegeleer
Summary: A method for detecting Streptococcal competence stimulating quorum sensing peptides in human saliva at the nanomolar level was developed using an anti-adsorption diluent. The study found that a small number of saliva samples contained these peptides, indicating the production of quorum sensing peptides by Streptococcus species in the human oral cavity.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Biochemical Research Methods
Frederick Verbeke, Nathan Debunne, Yorick Janssens, Bart De Spiegeleer, Evelien Wynendaele
Summary: By utilizing solid phase extraction and UHPLC-MS/MS method, RNPP quorum sensing peptides were successfully detected in wild-type murine feces samples, aiding in the understanding of bacterial communication mechanisms.
Article
Chemistry, Analytical
Sultan Suleman, Sileshi Belew, Dereje Kebebe, Markos Duguma, Henok Teshome, Gemmechu Hasen, Evelien Wynendaele, Luc Duchateau, Bart De Spiegeleer
Summary: Quality-by-design (QbD) is a systematic approach based on science and quality risk management to design and develop products/services. It has been widely applied in the pharmaceutical industry but not well established in facilities like quality control laboratories. This study introduces the concept of laboratory QbD (lQbD) using the example of a water purification system in a drug quality laboratory. The established water purification system's capability was evaluated through routine monitoring of quality parameters and the quality of different grade water used in the laboratory.
INTERNATIONAL JOURNAL OF ANALYTICAL CHEMISTRY
(2022)
Article
Biology
Evelien Wynendaele, Nathan Debunne, Yorick Janssens, Anton De Spiegeleer, Frederick Verbeke, Liesa Tack, Sophie Van Welden, Evy Goossens, Daniel Knappe, Ralf Hoffmann, Christophe Van De Wiele, Debby Laukens, Peter Van Eenoo, Lars Vereecke, Filip Van Immerseel, Olivier De Wever, Bart De Spiegeleer
Summary: This study identifies quorum sensing peptides as potential regulators of host-microbe interactions and demonstrates that a metabolite of an EntF peptide promotes colorectal cancer metastasis in vivo. These findings provide a starting point for further investigation into the role of the microbiome in colorectal cancer metastasis and the development of novel biotherapeutics in other disease areas.
Article
Infectious Diseases
Fanta Gashe, Evelien Wynendaele, Bart De Spiegeleer, Sultan Suleman
Summary: This study evaluated the stabilizing effects of phosphate buffer and mannitol against short-term artesunate hydrolysis, with results indicating that phosphate buffer was the main stability determining factor of artesunate in the aqueous intravenous (i.v.) formulation, while mannitol lacked stabilizing effect.
Article
Oncology
Anton De Spiegeleer, Evelien Wynendaele, Amelie Descamps, Nathan Debunne, Bart P. Braeckman, Marjan De Mey, Julie Coudenys, Liesbeth Crombez, Frederick Verbeke, Yorick Janssens, Rekin's Janky, Evy Goossens, Caroline Vlaeminck, Dries Duchi, Vanessa Andries, Emilie Dumas, Mirko Petrovic, Tom van de Wiele, Daniel Knappe, Ralf Hoffmann, Vincent Mouly, Anne Bigot, Lars Vereecke, Filip Van Immerseel, Nele van den Noortgate, Bart De Spiegeleer, Dirk Elewaut
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Anton De Spiegeleer, Amelie Descamps, Srinath Govindarajan, Julie Coudenys, Kevin van der Borght, Hannah Hirmz, Nele van den Noortgate, Dirk Elewaut, Bart De Spiegeleer, Evelien Wynendaele
Summary: This study discovered the potential of quorum-sensing peptides to modulate the immune system in microbiome-host interactions. Through screening 89 peptides, four of them were found to activate immune cells in vitro, and one of them was detected in human plasma. These findings are biologically significant and reveal the immunomodulatory potential of quorum-sensing peptides.
Article
Chemistry, Analytical
Iro Konstantina Ventouri, Wayne Chang, Florian Meier, Roland Drexel, Govert W. Somsen, Peter J. Schoenmakers, Bart de Spiegeleer, Rob Haselberg, Alina Astefanei
Summary: We developed an online analytical platform combining asymmetrical flow field-flow fractionation (AF4) with native mass spectrometry (nMS) for studying labile higher-order structures (HOS) of protein biotherapeutics. The platform also utilizes UV absorbance, multi-angle light scattering (MALS), and differential refractive-index (UV-MALS-dRI) detectors. We studied the stability and dissociation pathways of the tetrameric biotherapeutic enzyme L-asparaginase (ASNase) and found the presence of intact octamers and degradation products using AF4-MALS/nMS. Exposure of ASNase to high pH disrupted the equilibrium between non-covalent species and led to HOS dissociation. The developed platform provides valuable insights for aggregation and stability studies of protein biopharmaceuticals.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Amelie Descamps, Kevin Van der Borght, Anton De Spiegeleer, Evelien Wynendaelea, Bart De Spiegeleer
Summary: To improve the translation of peptidomic research, it is crucial to detect peptides at low levels in biofluids. This study investigates often neglected parts of the analytical process and proposes novel approaches for sample collection, preparation, chromatography, and MS detection. The recommendations provided will enhance the reliability of peptidomics bio-analytics.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Hannah Hirmz, Frederick Verbeke, Bartosz Wielgomas, Christophe Furman, Emmanuelle Lipka, Bart De Spiegeleer, Evelien Wynendaele
Summary: Green chemistry initially focused on organic synthetic approaches, and now green analytics is also seeking ways to reduce volumes, cost, and ecotoxicity of analytically used chemicals and lower energy usage. The current emphasis is on techniques like miniaturization, on-line spectroscopy, and chemicals used in the analytical process. However, little attention has been given to the production and use of analytical reagents in greening analytics.
SUSTAINABLE CHEMISTRY AND PHARMACY
(2023)