Article
Materials Science, Multidisciplinary
Fabien Granier, Sebastien Marie, Zahra Al Amir Dache, Julien Aityaya, Thibault Mazard, Laurent Garrelly, Corinne Prevostel
Summary: This study provides an in vitro methodology to assess the cytotoxicity and cell penetration of dendrigrafts of poly-L-lysine (DGLs) for potential use as nanoscale drug carriers for cancer treatment. The data suggests that DGLs exhibit cytotoxicity comparable to other dendrimers, are taken up by cancer cells quickly, and serum components can reduce their cytotoxicity.
ACS APPLIED POLYMER MATERIALS
(2022)
Article
Materials Science, Multidisciplinary
Ying Lu, Zuojia Xiang, Ning Li, Xiaobo Huang, Jianbo Song
Summary: In this study, a photocurable bioink composed of modified EPL-MA was developed for DLP 3D printing. Using DLP technology, highly complex organ model structures can be built with excellent reliable biocompatibility.
Article
Biotechnology & Applied Microbiology
Xinglin Jiang, Yulia Radko, Tetiana Gren, Emilia Palazzotto, Tue Sparholt Jorgensen, Tao Cheng, Mo Xian, Tilmann Weber, Sang Yup Lee
Summary: epsilon-Poly-L-lysine, a potent antimicrobial produced from Streptomyces, is widely distributed in cheese and human skin bacteria, suggesting its role as a bioactive secondary metabolite in cheese and skin ecosystems. This discovery raises the possibility of epsilon-Poly-L-lysine naturally existing in cheese and on human skin. The gene responsible for producing epsilon-Poly-L-lysine is found in various coryneform actinobacteria isolated from cheese and human skin, indicating that its production is not limited to filamentous actinobacteria.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Sijin Chen, Shuting Huang, Yan Li, Chuncai Zhou
Summary: This review summarized the advanced development in the synthesis and modification strategies of ε-poly-L-lysine (EPL) and lysine-based dendrimer (LBD) compounds, focusing on their applications in biomedical fields such as agents, adjuvants, and carriers for anti-pathogen, tumor, and gene therapies. The combination with other advanced methodologies and technologies shows potential for overcoming challenges like scale production and high expenses in the future development of lysine-based polymers.
FRONTIERS IN CHEMISTRY
(2021)
Article
Microbiology
Liang Wang, Hao Yang, Mengping Wu, Jianhua Zhang, Hongjian Zhang, Zhonggui Mao, Xusheng Chen
Summary: This study comprehensively analyzed the biosynthetic mechanisms of epsilon-PL in S.albulus WG-608 through integrated physiological, transcriptomic, and proteomic association analysis. The results revealed differential expression of key genes in various metabolic pathways, leading to increased carbon flux into L-lysine biosynthesis and epsilon-PL production. Furthermore, changes in the regulation of DNA replication, transcription, and translation, as well as quorum sensing, were observed, potentially contributing to environmental adaptability and epsilon-PL biosynthesis. Overexpression of the ppk gene and addition of polyP(6) further enhanced epsilon-PL production.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Angel Espinoza-Gonzalez, Carmen Hernandez-Valencia, Luis Cedeno-Caero, Roberto Sanchez-Sanchez, Carmina Montiel, Miquel Gimeno
Summary: Subtilisin Carlsberg, an alkaline protease from Bacillus licheniformis, can catalyze the synthesis of high molecular weight cationic alpha-poly-L-lysine and amphiphilic poly(alpha-L-lysine-co-L-phenylalanine) in organic solvent. The reaction is conducted in hydrophobic non-toxic 1,1,1,2-tetrafluoroethane solvent, and the low water environment limits hydrolysis of the peptide chains. The organic compressed fluid used in the reaction has low-pressure requirements and evaporates completely after the reaction, leaving no solvent residues. The resulting polypeptides show no cytotoxicity in human cells.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Jie Yu, Danwei Cen, Yongcheng Chen, Hailan Zhao, Mengyue Xu, Sulan Wu, Shuo Wang, Qiao Jin, Ting Shen
Summary: Antibiotic resistance poses a significant threat to public health, and improving the therapeutic efficacy of conventional antibiotics is an effective solution. By conjugating the positively charged epsilon-poly-l-lysine to erythromycin, the modified EPL-EM showed enhanced antibacterial activity and reduced drug resistance development. Furthermore, EPL-EM exhibited excellent biocompatibility without inducing hemolysis and cytotoxicity.
Article
Biotechnology & Applied Microbiology
Gavin Gonzales, Jiaul Hoque, Anna Gilpin, Biswanath Maity, Stefan Zauscher, Shyni Varghese
Summary: This study focuses on the development of cationic nanocarriers to overcome the challenges of drug delivery to cartilage tissue. These nanocarriers, which adhere quickly to cartilage tissue and can penetrate and remain within its full thickness, show promising results for therapeutic outcomes.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Engineering, Biomedical
Paniz Memarian, Atefeh Solouk, Zohreh Bagher, Somaye Akbari, Masoumeh Haghbin Nazarpak
Summary: Poly (l-lactic acid) (PLLA) electrospun nanofibrous scaffolds were modified by blending with second-generation poly amidoamine (PAMAM) to enhance their ionic conductivity and water absorption. The presence of PAMAM increased fiber diameter, crystallinity, hydrophilicity, water absorption, elongation-at-break, and cell viability. The conductivity of the scaffolds was enhanced by about nine times by increasing the amount of PAMAM. The results suggest that PAMAM can improve the limitations of PLLA and enhance its performance in biomaterial applications.
BIOMEDICAL MATERIALS
(2022)
Article
Chemistry, Applied
Hao Wu, Shuqian Hu, Chunling Nie, Jiahui Zhang, Huafeng Tian, Weicheng Hu, Ting Shen, Jianguo Wang
Summary: A novel method was described for synthesizing antibacterial cellulose beads, which exhibited excellent antimicrobial activity and biodegradability, showing great potential for use in food and environmental applications.
CARBOHYDRATE POLYMERS
(2021)
Review
Biotechnology & Applied Microbiology
Liang Wang, Chongyang Zhang, Jianhua Zhang, Zhiming Rao, Xueming Xu, Zhonggui Mao, Xusheng Chen
Summary: The review compares traditional and advanced strategies for discovering and cultivating high-producing strains of epsilon-poly-L-lysine, including traditional methods based on isolation and culture, genome mining, and directed evolution. Additionally, process engineering methods for improving production and efficient downstream purification methods are discussed in the article.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Agronomy
Jingjing Wu, Jingjing Hu, Wenxiao Jiao, Yamin Du, Cong Han, Qingmin Chen, Xin Chen, Maorun Fu
Summary: The study found that e-PL had a better inhibitory effect on C. gloeosporioides, reducing the expansion of anthracnose in various plants and affecting spore germination, mycelia morphology, and cell membrane integrity. Furthermore, e-PL caused membrane damage of C. gloeosporioides, leading to leakage of cell contents and mitochondrial damage, while also regulating organic acid metabolism. These findings demonstrate that e-PL can effectively inhibit C. gloeosporioides through membrane targeting and metabolic regulation.
POSTHARVEST BIOLOGY AND TECHNOLOGY
(2023)
Article
Chemistry, Applied
Chunling Nie, Ting Shen, Weicheng Hu, Qin Ma, Jiahui Zhang, Shuqian Hu, Huafeng Tian, Hao Wu, Xiaogang Luo, Jianguo Wang
Summary: In this study, cellulose beads grafted with epsilon-poly-L-lysine were prepared through chemical reactions. The grafted beads showed strong antibacterial activities and biodegradability, indicating potential applications in water purification and food treatment fields.
CARBOHYDRATE POLYMERS
(2021)
Article
Biochemistry & Molecular Biology
V. S. Pokrovsky, A. N. Lukashev, G. Babayeva, S. Sh Karshieva, A. Yu Arinbasarova, A. G. Medentzev, M. Komarova, E. Lukasheva
Summary: Pharmacokinetic studies on L-lysine alpha-oxidase (LO) revealed its potential as a promising enzyme for further investigation as a potential anticancer agent, due to its antitumor, antimicrobial, and antiviral properties.
Article
Chemistry, Applied
Cong Wang, Hui Cao, Lingyun Jia, Wenli Liu, Pengtao Liu
Summary: This study designed an aerogel material using TOCNF/ε-PL network and citric acid as the cross-linking agent. Experimental results showed that the aerogel had good mechanical properties, antibacterial effects, biodegradability, and blood compatibility, indicating great potential applications in medical and food packaging fields.
CARBOHYDRATE POLYMERS
(2022)
Article
Chemistry, Physical
Stephanie MacWilliams, Andrew J. Clulow, Nigel M. Kirby, Reinhard Miller, Ben J. Boyd, Graeme Gillies, David A. Beattie, Marta Krasowska
Summary: This study investigated the impact of dairy proteins on interfacial mono-and diglycerides (MDG) crystal formation using interfacially-sensitive techniques. The results showed that dairy proteins can lower the temperature at which MDG crystals form at the oil-water interface, and the displacement of proteins during interfacial crystal formation was observed. Additionally, X-ray scattering techniques were used to characterize lipid crystals formed at the oil-water interface for the first time, and the results demonstrated that protein adsorption does not affect the MDG crystal structures. Therefore, the informed selection of emulsifier components is crucial for controlling interfacial crystallization and its impact on emulsion stability.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Adam Markowski, Magdalena Zaremba-Czogalla, Anna Jaromin, Ewa Olczak, Adrianna Zygmunt, Haniyeh Etezadi, Ben J. Boyd, Jerzy Gubernator
Summary: Pancreatic cancer is a deadly disease, and there is an urgent need for new drugs and therapies. Liposome-based formulations of naturally-derived bioactive compounds show promise as anticancer candidates due to their ability to accumulate in tumor tissues and protect against toxicity. In this study, the naturally-derived flavonoid baicalein was encapsulated in a liposomal bilayer with high efficiency. The resulting formulation showed stability and demonstrated cytotoxic activity against pancreatic cancer cell lines, making it a potential candidate for anti-PDAC therapy.
Article
Biochemistry & Molecular Biology
Yuen Yi Lam, Angel Tan, Cameron J. Nowell, Kristian Kempe, Ben J. Boyd
Summary: Metabolic oligosaccharide engineering (MOE) allows the introduction of functionality to cell membranes through synthetic monosaccharides. MOE enables the expression of unnatural sugars (e.g., peracetylated mannose-azide) on cell surfaces, and the azide group can participate in a copper-free click reaction with an alkyne probe (e.g., dibenzocyclooctyne, DBCO), providing insights into monosaccharide metabolism in cells.
Article
Biochemistry & Molecular Biology
Patrick Tai, Andrew J. Clulow, Ben J. Boyd, Matt Golding, Harjinder Singh, David W. Everett
Summary: Sphingomyelin and cholesterol in the milk fat globule membrane form functional liquid-ordered domains. These domains resist digestion by bile and play a crucial role in gastrointestinal digestion. By using small-angle X-ray scattering, the structural changes in various model bilayer systems were investigated upon interaction with bovine bile. The results showed that the complexation of sphingomyelin with cholesterol can inhibit the disruption of vesicles by bile at lower cholesterol concentrations. The swelling of biliary mixed micelles was influenced by the cholesterol concentration, with less swelling observed at higher cholesterol concentrations. The importance of these findings is discussed.
CHEMISTRY AND PHYSICS OF LIPIDS
(2023)
Article
Pharmacology & Pharmacy
Renae K. Barr, Bryce W. Barber, Jessica R. Tait, Cornelia B. Landersdorfer, Sam Salman, Gabrielle C. Musk, Madhu Page-Sharp, Kevin T. Batty, Joseph Kado, Laurens Manning, Jonathan R. Carapetis, Ben J. Boyd
Summary: Regular intramuscular injections of benzathine penicillin G (BPG) have been the main method for secondary prophylaxis of rheumatic heart disease (RHD) since the 1950s. However, patient adherence is poor due to pain, the need for regular injections, and challenges in resource-limited settings. A slow release implant with extended treatment duration could be a potential alternative.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Wenxiao K. Yue, Tianxia Zhang, Rekha Shandre Mugan, Nicholas Barlow, David K. Chalmers, Colin W. Pouton, Philip E. Thompson
Summary: Various strategies for peptide macrocyclization often require orthogonal protection or offer limited structural diversification. We have developed an efficient macrocyclization method using nucleophilic aromatic substitution to create thioether macrocycles. This versatile macrocyclization can be performed on unprotected peptidomimetics or resin-bound peptides, allowing for further modification and addition of functional groups. By applying this strategy, a library of potent melanocortin agonists with distinct subtype selectivity was successfully designed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Alina D. Lam, Ian K. Styles, Danielle Senyschyn, Enyuan Cao, Abel Anshabo, Mohammad Abdallah, Reyaj Mikrani, Cameron J. Nowell, Christopher J. H. Porter, Orlagh M. Feeney, Natalie L. Trevaskis
Summary: Changes in immune cells within the joint-draining lymphatics contribute to the progression of inflammatory arthritis. There is an expansion of pathogenic B cells in the joint-draining lymph node, which inhibit lymph flow and reduce clearance of inflammatory fluid and cells. Localized delivery of B-cell depleting therapies to the joint-draining lymph nodes has the potential to improve treatment efficacy and reduce side effects.
MOLECULAR PHARMACEUTICS
(2023)
Editorial Material
Medicine, Research & Experimental
Orlagh M. Feeney, Christopher J. H. Porter, Kara L. Vine
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Mahta Mansouri, Shawn Rumrill, Shane Dawson, Adam Johnson, Jo-Anne Pinson, Menachem J. Gunzburg, Catherine F. Latham, Nicholas Barlow, George W. Mbogo, Paula Ellenberg, Stephen J. Headey, Nicolas Sluis-Cremer, David Tyssen, Joseph D. Bauman, Francesc X. Ruiz, Eddy Arnold, David K. Chalmers, Gilda Tachedjian
Summary: Human immunodeficiency virus type I (HIV-1) is a major global health burden, and the emergence of drug-resistance mutations necessitates the development of novel drugs. In this study, a fragment-based drug discovery approach was used to optimize a hit fragment (compound B-1) that targets the viral protein reverse transcriptase (RT) in a novel site. Different compound series were synthesized and evaluated for their RT binding and inhibition, leading to the identification of a lead compound with promising inhibitory activity. This study offers a starting point for the development of novel dual inhibitors targeting the NNRTI-binding pocket and an adjacent site.
Article
Nanoscience & Nanotechnology
Syaza Y. Binte Abu Y. Bakar, Malinda Salim, Andrew J. Clulow, Susanne Seibt, Cornelia B. Landersdorfer, Donna T. Geddes, Kevin R. Nicholas, Ben J. Boyd
Summary: Colostrum provides essential bioactive components for the infant gut microbiota colonization and preventing infectious diseases. However, substitutes are urgently needed for premature infants when colostrum is unavailable. This study aimed to design an appropriate lipid component for a colostrum substitute and evaluate its ability to reduce inflammation in intestinal cells. Analysis showed that the digestion of colostrum and the substitute mixtures had similar lipid profiles but exhibited subtle differences in self-assembly behavior. Bifidobacteria cultured on the substitute mixtures modulated the biological markers of necrotizing enterocolitis, suggesting the potential of these substitutes in reducing the characteristics associated with this disease.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Chiara Pasquarella, Serena Bertoni, Nadia Passerini, Ben J. Boyd, Karlis Berzins
Summary: This study evaluated the performance of different spectral ranges in the kinetic in situ analysis of lipid polymorphic transformations and found that the low-frequency Raman (LFR) domain showed superior characteristics and structural sensitivity.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Medicine, Research & Experimental
Anas Aljabbari, Shinji Kihara, Thomas Rades, Ben J. Boyd, Karlis Berzins
Summary: The adsorption of gut relevant biomolecules onto particles after oral administration of solid oral dosage forms is expected to form a gastrointestinal corona, which could influence solution-mediated solid-state transformations. This study used low-frequency Raman spectroscopy to investigate the in situ solid-state phase transformations under biorelevant conditions and the presence of biomolecules. The results showed a change in the solid-state transformation pathway from amorphous to crystalline drug and the role of biomolecules in influencing these transformations.
MOLECULAR PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Malinda Salim, Sara J. Fraser-Miller, Karlis Berzins, Joshua J. Sutton, Keith C. Gordon, Ben J. Boyd
Summary: Low-frequency Raman spectroscopy (LFRS) is used to detect and track the precipitation of drugs in lipid-based formulations during digestion. Multivariate data analysis and univariate analysis approaches were used to analyze the spectral changes over time and compare the results with small angle X-ray scattering (SAXS) measurements. LFRS was found to be a complementary technique to determine the kinetics of drug precipitation from lipid-based formulations, potentially providing more accessible results than SAXS.
Article
Pharmacology & Pharmacy
Alexander J. Martin, David M. Shackleford, Susan A. Charman, Kylie M. Wagstaff, Christopher J. H. Porter, David A. Jans
Summary: This study evaluated the in vivo exposure of 4-HPR and developed lipid-based formulations to enhance its exposure. Pharmacokinetic analysis showed that clinical formulation achieved effective plasma concentrations, while novel formulations achieved more than 3-fold improvement. However, solubility and first-pass intestinal elimination limited the exposure, which could be improved through CYP inhibition. Simulated exposure profiles suggested that b.i.d dosage regime with clinical formulation and new formulations/CYP inhibition were viable options to increase exposure.
Article
Chemistry, Medicinal
Wenxiao K. Yu, Tianxia Zhang, Rekha Shandre Mugan, Nicholas Barlow, David K. Chalmers, Colin W. Pouton, Philip E. Thompson
Summary: We have developed an efficient macrocyclization method utilizing nucleophilic aromatic substitution to create thioether macrocycles. This strategy is versatile and can be applied to unprotected peptidomimetics or resin-bound peptides. The resulting electron-withdrawing groups can be further used for orthogonal reactions, allowing for diversification and alteration of peptide properties. We applied this macrocyclization strategy to design melanocortin ligands, successfully generating a library of potent and selective agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
