Review
Pharmacology & Pharmacy
Andreea Gostaviceanu, Simona Gavrilas, Lucian Copolovici, Dana Maria Copolovici
Summary: Membrane-active peptides (MAPs) have unique properties that make them valuable tools for studying membrane structure and function and promising candidates for therapeutic applications. They can selectively interact with multiple membranes and disrupt lipid bilayers through different pathways. MAPs have shown antimicrobial activity, selective targeting of cancer cells, and drug delivery capabilities, making them a fascinating class of biomolecules with significant potential in basic research and clinical applications.
Review
Infectious Diseases
Andreas Hadjicharalambous, Nikolaos Bournakas, Hector Newman, Michael J. J. Skynner, Paul Beswick
Summary: This review examines the mechanisms of antimicrobial peptides in translocating across bacterial membranes and proposes strategies for combating antimicrobial resistance. By understanding the interactions between peptides and biological membranes, new peptide vectors may be developed for delivering antibiotics.
Article
Infectious Diseases
Oktawian Stachurski, Damian Neubauer, Aleksandra Walewska, Emilia Ilowska, Marta Bauer, Sylwia Bartoszewska, Karol Sikora, Aleksandra Hac, Dariusz Wyrzykowski, Adam Prahl, Wojciech Kamysz, Emilia Sikorska
Summary: This study investigates short cationic antimicrobial lipopeptides with a high propensity to fibrillate, which exhibit high activity and stability on bacterial membranes, and low cytotoxicity against human cells. The findings suggest that monomers are the main active form and the target of action of the lipopeptides is the bacterial membrane.
Article
Engineering, Biomedical
Hui Shao, Jin Zhou, Xiaoqian Lin, Yue Zhou, Yumeng Xue, Weili Hong, Xubo Lin, Xiaoling Jia, Yubo Fan
Summary: Developing new antimicrobial agents to combat drug-resistant pathogens and biofilms is an urgent task. Cationic antimicrobial peptides (AMPs) have potential due to their unique membrane rupture mechanism, but their high toxicity and low stability limit their application. In this study, a biomimetic strategy was used to construct cationic peptide-conjugated liposomes, inspired by cell-penetrating peptides (CPPs), to enhance antibacterial efficacy and biosafety. Computational simulation and experimental investigations identified the optimal peptide-conjugated liposomes, which showed enhanced antibacterial efficacy without compromising cytotoxicity. This bio-inspired design could contribute to the development of next-generation antimicrobials.
Article
Pharmacology & Pharmacy
Corina Ciobanasu
Summary: Membrane active peptides have potential in targeted drug delivery systems, and understanding their uptake mechanism is crucial for peptide therapeutics development and clinical use. By studying the dynamics and kinetics of peptides on model membranes, relevant information on peptide uptake steps can be obtained.
Article
Chemistry, Medicinal
Maria Angeles Abengozar, Maria Fernandez-Reyes, Vivian A. Salazar, Marc Torrent, Beatriz G. de la Torre, David Andreu, Ester Boix, Luis Rivas
Summary: Eosinophil cationic protein (ECP) can enter the cytoplasm of Leishmania parasites, leading to RNA degradation and playing a key role in parasite killing. ECP combines membrane destabilization and enzymatic activities to effect parasite killing.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Maria Angeles Abengozar, Maria Fernandez-Reyes, Vivian A. Salazar, Marc Torrent, Beatriz G. de la Torre, David Andreu, Ester Boix, Luis Rivas
Summary: The research suggests that eosinophils recruitment into Leishmania lesions may contribute to treatment. Eosinophil cationic protein (ECP) shows broad antimicrobial activity and enters the Leishmania cytoplasm leading to parasite killing through mechanisms such as RNA degradation.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Mingcong Niu, Xiulian Gu, Jingyi Yang, Haoyu Cui, Xinyi Hou, Yue Ma, Chunhua Wang, Guangcheng Wei
Summary: Bacterial drug resistance poses a serious threat, necessitating the development of effective antibacterial drugs. This study focused on the design and synthesis of glycolipidpeptides with excellent antibacterial and immunomodulatory activities, which exhibited sustained-release properties and combined sterilization effects. The results demonstrate the potential applications of this research.
Article
Chemistry, Multidisciplinary
Mingcong Niu, Xiulian Gu, Jingyi Yang, Haoyu Cui, Xinyi Hou, Yue Ma, Chunhua Wang, Guangcheng Wei
Summary: Bacterial drug resistance is a serious issue, and the development of effective antibacterial drugs is urgently needed. Antimicrobial peptides (AMPs) show great potential as candidates for fighting bacteria. In this study, a series of AMPs with specific biological characteristics were designed and synthesized. Among them, the glycolipidpeptide GLP6 demonstrated excellent antibacterial and immunomodulatory activity, stability, biocompatibility, biofilm eradication, and membrane penetrating activity.
Article
Pharmacology & Pharmacy
Sandra Patricia Rivera-Sanchez, Ivan Dario Ocampo-Ibanez, Yamil Liscano, Natalia Martinez, Isamar Munoz, Marcela Manrique-Moreno, Luis Martinez-Martinez, Jose Onate-Garzon
Summary: This study investigates the interaction between a cationic antimicrobial peptide (CAMP) derived from Cecropin D-like and bacterial-like model membranes of colistin-resistant Pseudomonas aeruginosa (CRPa) strains. The experimental analysis shows that the peptide interacts with the lipids of CRPa membranes, resulting in an increase in the phase transition temperature of the lipid systems and a transition in the peptide's secondary structure.
Article
Pharmacology & Pharmacy
Wioletta Brankiewicz, Joanna Okonska, Katarzyna Serbakowska, Jan Lica, Marek Drab, Natalia Ptaszynska, Anna Legowska, Krzysztof Rolka, Piotr Szweda
Summary: This study reported five conjugates composed of fluconazole and cell penetrating or antimicrobial peptide, showing high antifungal activity, especially against fluconazole-resistant strains, with low cytotoxicity.
Article
Chemistry, Multidisciplinary
Apurva Panjla, Grace Kaul, Abdul Akhir, Deepanshi Saxena, Saurabh Joshi, Chandrima Modak, Dipti Kumari, Alok Jain, Sidharth Chopra, Sandeep Verma
Summary: Antimicrobial resistance is a significant public health risk, and there is a need for novel antimicrobial compounds. In this study, cationic chlorpromazine peptide conjugates were found to effectively target multidrug-resistant bacteria, particularly MDR S. aureus. The most potent compound, CPWL, showed promising antibacterial activity without cytotoxicity. Molecular docking and MD simulation studies confirmed that CPWL specifically targeted S. aureus enoyl reductase (saFabI). These findings highlight cationic chlorpromazine as a promising scaffold for the development of saFabI inhibitors for severe staphylococcal infections.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Martina Bischetti, Nadine Alaimo, Francesca Nardelli, Pasqualina Punzi, Cristi Amariei, Raffaele Ingenito, Giovana Musco, Mariana Gallo, Daniel Oscar Cicero
Summary: Of-Pis1 is a potent antimicrobial peptide that selectively interacts with bacterial membranes, with low toxicity against human erythrocytes. Its interaction with bacterial membranes is tighter and structurally perturbs lipopolysaccharide micelles. Analysis of its amino acid sequence and composition can be used to design more potent and selective antimicrobial peptides.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Review
Pharmacology & Pharmacy
Adam Carrera-Aubesart, Maria Gallo, Sira Defaus, Toni Todorovski, David Andreu
Summary: Bioactive peptides have gained recognition in biomedical areas due to their unique interactions with biological membranes. Topoisomeric peptides, made up of D-amino acids, provide a way to overcome protease degradation and mimic native peptide structures. This review focuses on recent advances in topoisomeric peptides with therapeutic applications, such as drug delivery and antimicrobial and anticancer activities, and discusses their interactions with membrane targets.
Article
Chemistry, Multidisciplinary
Motoharu Hirano, Hidetomo Yokoo, Chihiro Goto, Makoto Oba, Takashi Misawa, Yosuke Demizu
Summary: We have developed cell-penetrating stapled peptides based on the amphipathic antimicrobial peptide magainin 2 for efficient intracellular delivery of nucleic acids including pDNA, mRNA, and siRNA. The peptide st7-5_R can form stable complexes with these nucleic acids and efficiently deliver them into cells.
Article
Chemistry, Multidisciplinary
Dana E. Moseson, Ayse Eren, Kevin J. Altman, Isaac D. Corum, Mingyue Li, Yongchao Su, Zoltan K. Nagy, Lynne S. Taylor
Summary: Particle engineering approaches were used to recrystallize drugs with different attributes, which were then processed into ASDs using hot melt extrusion. The study found that particle size and defect density significantly influenced the amorphization rate, with breakage kinetics playing a dominant role in the crystal dissolution process.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Medicine, Research & Experimental
Mingyue Li, Paul Reichert, Chakravarthy Narasimhan, Bradley Sorman, Wei Xu, Aaron Cote, Yongchao Su
Summary: Developing biological formulations to maintain the chemical and structural integrity of therapeutic antibodies is challenging. This study demonstrates the high-resolution characterization of mAb microcrystalline suspension using magic angle spinning NMR spectroscopy. The impact of thermal stress and dehydration on the structure, dynamics, and stability of the mAb crystals is evaluated. The study provides valuable structural details and insights into the cocrystallization of the protein and ligand.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Dana E. Moseson, Tze Ning Hiew, Yongchao Su, Lynne S. Taylor
Summary: Through matrix crystallization, an amorphous solid can transform into a more stable crystalline state, reducing the driving force for dissolution. This study investigated the mechanism of matrix crystallization in amorphous solid dispersions (ASDs) and examined its implications for formulation and process design. The results showed that systems with high drug loading, mechanical activation, and surfactants were at greater risk of matrix crystallization, while systems with rapid and congruent drug and polymer release had greater resistance to matrix crystallization.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Physical
Yong Du, Yongchao Su
Summary: Solid-state NMR is a powerful tool for characterizing drug substances and products. Fluorine-containing drugs offer the opportunity to use fluorine as a molecular probe for pharmaceutical analysis. This review highlights recent advancements of 19F magic angle spinning NMR methods in drug research and development.
SOLID STATE NUCLEAR MAGNETIC RESONANCE
(2022)
Article
Chemistry, Multidisciplinary
Tarun Tejasvi Mutukuri, Jing Ling, Yong Du, Yongchao Su, Qi Tony Zhou
Summary: This study investigated the impact of buffer salts on the physical stability of spray-dried and lyophilized formulations of bovine serum albumin (BSA). The results showed that buffer salts had less influence on the physical stability of spray-dried formulations compared to lyophilized solids. Conventional techniques showed no correlation with the physical stability. However, solid-state nuclear magnetic resonance spectroscopy successfully identified phase separation between the buffer component and protein in the lyophilized formulation.
PHARMACEUTICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Jing Song, Guangli Hu, Hassen Hamzaoui, Yogita Krishnamachari, Steven C. Persak, Hanmi Xi, Yongchao Su
Summary: This study compares the impact of storage time on silicone oil migration in siliconized syringes from different manufacturers. The research finds that there is a 2.5-fold increase in subvisible particle count and up to a 2-fold increase in extrusion force in fresh syringes compared to aged ones. These findings suggest that the storage time prior to filling affects the degree and amount of silicone oil migration.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Editorial Material
Medicine, Research & Experimental
Yongchao Su
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Analytical
Yong Du, Jochem Struppe, Barbara Perrone, Alia Hassan, Anna Codina, Yongchao Su
Summary: This study demonstrates the application of CPMAS CryoProbe technology to improve the sensitivity of C-13 and N-15 detection in solid-state analysis of pharmaceutical drug posaconazole. The enhanced sensitivity enables resonance assignment and structural elucidation through 2D C-13-C-13 and H-1-N-15 correlation experiments. The results reveal drug-drug and drug-polymer interactions in amorphous POSA and its solid dispersion formulation.
Review
Chemistry, Multidisciplinary
Yusuke Nishiyama, Guangjin Hou, Vipin Agarwal, Yongchao Su, Ayyalusamy Ramamoorthy
Summary: Solid-state NMR spectroscopy is a commonly used technique for studying the atomic-resolution structure and dynamics of various systems. However, its spectral resolution and sensitivity have been limited. The development of ultrafast-MAS technology has provided opportunities to improve the resolution and sensitivity of solid samples. Despite the limitations and challenges, ultrafast-MAS NMR techniques have achieved remarkable results in various fields.
Article
Chemistry, Multidisciplinary
Marc B. Taraban, Katharine T. Briggs, Yihua Bruce Yu, Michael T. Jones, Lindsey Rosner, Akhilesh Bhambhani, Donna M. Williams, Christopher Farrell, Mikhail Reibarkh, Yongchao Su
Summary: This study utilizes wNMR technology to evaluate the stability of aluminum adjuvants and antigen-adjuvant complexes under physical stresses, including gravitation, flow, and freeze/thaw. The results obtained from wNMR are confirmed by conventional analytical techniques such as static light scattering and microfluidic imaging. The findings demonstrate that wNMR can rapidly and noninvasively determine whether aluminum adjuvants or antigen-adjuvant complexes have been altered by physical stresses.
PHARMACEUTICAL RESEARCH
(2023)
Article
Chemistry, Physical
Deyun Wang, Yongchao Su, Kang Chen
Summary: Knowledge of molecular rotational dynamics is crucial for understanding solution NMR spectroscopy. The study finds that the observed NMR signals in micelles contradict the viscosity effects predicted by the SED equation. By measuring the spin relaxation rates of a drug dissolved in micelles, the study demonstrates fast rotational dynamics of the solute molecules inside micelles, highlighting the role of intermolecular interactions rather than solvent viscosity in governing molecular motion.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Zhaoxi Zheng, Yongchao Su, Klaus Schmidt-Rohr
Summary: This study corrected the peak assignments in the solid-state C-13 NMR spectrum of HPMCAS using quantitative spectra, spectral editing, empirical chemical-shift predictions, and full spectrum simulation. The study also quantified the side-group concentrations in different grades of HPMCAS.
MAGNETIC RESONANCE IN CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Brian Wong, Xi Zhao, Yongchao Su, Hanlin Ouyang, Timothy Rhodes, Wei Xu, Hanmi Xi, Dan Fu
Summary: Particles in biopharmaceutical products pose risks to product quality and safety. Existing analytical techniques lack the sensitivity and resolution to detect small particles and provide chemical information. In this study, we use stimulated Raman scattering microscopy to monitor proteinaceous particles and silicone oil droplets in a prefilled syringe barrel, overcoming these challenges. Our method allows for quantification and classification of particles in protein therapeutics with chemical and spatial information.
MOLECULAR PHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Zhenxuan Chen, Haichen Nie, Chris J. Benmore, Pamela A. Smith, Yong Du, Stephen Byrn, Allen C. Templeton, Yongchao Su
Summary: The structural investigation of amorphous pharmaceuticals is crucial for understanding their stability, but has been underexplored due to limited analytical tools. In this study, X-ray pair distribution functions and solid-state nuclear magnetic resonance techniques were used to probe the molecular packing of amorphous posaconazole. The findings provide insights into the intermolecular interactions and highlight the efficacy of combining X-ray PDF and ssNMR techniques for high-resolution exploration of amorphous structures.
MOLECULAR PHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Yong Du, Jinghan Li, Wei Xu, Aaron Cote, Ashley Lay-Fortenbery, Raj Suryanarayanan, Yongchao Su
Summary: Solid-state nuclear magnetic resonance spectroscopy (ssNMR) is used to analyze the phase and state transitions in pharmaceutical frozen solutions. It can identify crystallization, measure pH and water content, and provide insights into the rational development of biopharmaceuticals.
MOLECULAR PHARMACEUTICS
(2023)