Article
Biochemistry & Molecular Biology
Qi Hu, Haozhen Hu, Xinyi Zhang, Kyle Fan, Yuning Hong, Colin L. Raston, Youhong Tang
Summary: This study demonstrated the manipulation of protein unfolding/refolding for beta-lactoglobulin using thin film microfluidic vortex fluidic device (VFD) and monitored the process with an aggregation-induced emission luminogen (AIEgen), TPE-MI. The VFD accelerated denaturation reaction in the presence of denaturant, while rapid renaturation occurred without denaturant. The novel TPE-MI reacted with exposed cysteine thiol during protein unfolding, providing an easy and accurate way to monitor protein folding.
Article
Multidisciplinary Sciences
Philip To, Yingzi Xia, Sea On Lee, Taylor Devlin, Karen G. Fleming, Stephen D. Fried
Summary: The process of protein folding is complex and important, involving cellular factors and processes. Researchers have developed a new method to monitor the structural changes of Escherichia coli proteins in the cell cytosol and with chaperones. The results show that GroEL can assist in refolding the majority of proteins, while DnaK and GroEL have a similar set of proteins that they refold. Additionally, some proteins are not able to be refolded with any chaperones.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biotechnology & Applied Microbiology
Mariana N. Sao Pedro, Marieke E. Klijn, Michel H. M. Eppink, Marcel Ottens
Summary: The transition to continuous biomanufacturing aims to reduce costs and improve process robustness in the biopharmaceutical industry by utilizing miniaturized biosensors for real-time measurement of mAb aggregation during downstream processing.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kobe Janssen, Filip Claes, Dido Van de Velde, Vanessa L. Wehbi, Bert Houben, Yulia Lampi, Mieke Nys, Laleh Khodaparast, Ladan Khodaparast, Nikolaos Louros, Rob van der Kant, Joffre Verniers, Teresa Garcia, Meine Ramakers, Katerina Konstantoulea, Katerina Maragkou, Ramon Duran-Romana, Monica Musteanu, Mariano Barbacid, Bernard Scorneaux, Els Beirnaert, Joost Schymkowitz, Frederic Rousseau
Summary: Mutant KRAS is a challenging target for classical small molecule drugs, but this study shows that its misfolding can be induced by synthetic peptides derived from specific regions of the oncoprotein. These peptides were able to inhibit the function of mutant KRAS and showed antiproliferative activity against cancer cells. The findings provide proof-of-concept for exploiting the intrinsic misfolding propensity of KRAS as a therapeutic strategy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
C. Helbig, T. Menzen, K. Wuchner, A. Hawe
Summary: Imaging flow cytometry (IFC) is a technique for cellular imaging that allows parallel acquisition of data in brightfield, fluorescence, and side scattering channels. It has been applied to sub-visible particle analysis in biopharmaceuticals and has the potential to provide additional information, such as particle origin. This study developed masks for IFC image analysis to optimize the accuracy of size determination for polystyrene beads and pharmaceutically relevant particles in brightfield and fluorescence channels. The results showed good agreement between IFC and flow imaging microscopy (FIM) in terms of particle sizing, but IFC reported lower concentrations for polystyrene particle standards than FIM. For fluorescently stained silicone oil and protein particles, IFC FL imaging reported higher particle concentrations in the low micrometer size range. Overall, IFC is identified as a useful tool for generating supportive data for particle characterization purposes or trouble shooting activities, but not as a routine quantitative technique for subvisible particle analysis in drug product development or quality control.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jordan Bye, Kiah Murray, Robin Curtis
Summary: This study demonstrates that small multivalent polyphosphate ions, such as ATP and TPP, can overcome the trade-off between aggregation resistance and conformational stability caused by rational mutagenesis to supercharge proteins. These ions effectively increase protein colloidal stability by binding and overcharging the protein, thereby reducing aggregate growth. Further exploration of the potential of these ions as excipients for stabilizing biopharmaceuticals is warranted, especially in understanding the role of electrostatic interactions in maintaining protein stability in vivo.
Article
Chemistry, Medicinal
Alexandra Roesch, Sarah Zoells, Daniela Stadler, Constanze Helbig, Klaus Wuchner, Gideon Kersten, Andrea Hawe, Wim Jiskoot, Tim Menzen
Summary: Particles in biopharmaceutical formulations have been a hot topic in drug product development. This review provides a comprehensive overview of novel particle analysis techniques for particulate impurities in therapeutic protein formulations and biopharmaceutical formulations, discussing their applications, specific analytical approaches, and the advantages and drawbacks of currently available techniques.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Analytical
Yi-Yan Bai, Zhi-Tao Feng, Yan-Ju Yang, Xiao-Yan Yang, Zhi-Ling Zhang
Summary: This study utilized current lifetime as a dynamic parameter to distinguish differently sized nanoparticles successfully. By considering current lifetime instead of current intensity, more accurate evaluation of nanoparticle sizes can be achieved.
ANALYTICAL CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Jan Niklas Pauk, Janani Raju Palanisamy, Julian Kager, Krisztina Koczka, Gerald Berghammer, Christoph Herwig, Lukas Veiter
Summary: Overexpression of recombinant proteins in Escherichia coli can lead to the formation of inclusion bodies, but these are now being viewed as a promising production method. Refolding is necessary to obtain the correct active protein product, but current technology faces challenges like buffer usage, mixing uniformity, and low re-folding yields. Quality by Design methods, online monitoring techniques, and digital twin technology may offer a solution to these challenges.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Physical
Wenbo Zhang, Mingwei Liu, Lanlan Yu, Shanshan Mo, Zhun Deng, Shuli Liu, Yanlian Yang, Chen Wang, Chenxuan Wang
Summary: This study demonstrates the contribution of various noncovalent interactions to supramolecular assembly by investigating the self-assembly of peptides.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Multidisciplinary Sciences
Kimberly Jia Yi Low, Anandalakshmi Venkatraman, Jodhbir S. Mehta, Konstantin Pervushin
Summary: Protein aggregation and deposition in the form of amyloid fibrils is a characteristic feature of amyloid diseases. While most research focuses on inhibiting amyloid formation, it is equally important to understand the disaggregation mechanisms and their potential therapeutic applications. This review compiles the known mechanisms of amyloid disaggregation and explores the use of disaggregases for treating amyloidosis.
JOURNAL OF ADVANCED RESEARCH
(2022)
Article
Environmental Sciences
Yongyang Su, Guanyi Wei, Wei Wang, Ruiyang Xi, Xi Wang, Jiang Xu, Zhiming Li
Summary: This study evaluates the analytical performance of the commercial Hexin Single particle aerosol mass spectrometer (SPAMS) and extends its application. A universal method for particle size calibration, measurement, and correction is proposed, and isotope measurement is performed. The results show that the achieved accuracy of the isotope ratio for the elements investigated is 5%, and the instrument performance is relatively poor for elements with high ionization potential or bond energy. Additionally, the analysis of suspension particles confirms the effectiveness of the instrument and provides valuable information.
ATMOSPHERIC ENVIRONMENT
(2023)
Review
Biochemistry & Molecular Biology
Azadeh Beygmoradi, Ahmad Homaei, Roohullah Hemmati, Pedro Fernandes
Summary: Protein folding is a process that determines the three-dimensional structure of a protein. Recombinant protein production can face problems like proteolysis, incorrect folding, and protein aggregation. Identifying proper protein refolding conditions is challenging, and molecular chaperones can help in proper folding. Proper protein folding is essential for post-translational modifications, and incorrect folding can lead to cellular damage. Understanding recombinant protein expression and addressing folding issues are important.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Biochemistry & Molecular Biology
Alexey S. Morgunov, Kadi L. Saar, Michele Vendruscolo, Tuomas P. J. Knowles
Summary: Protein function relies on inter-molecular interactions occurring between proteins in various conformational states and levels of disorder, forming structures that can range in size and driving biological processes. Understanding the parameters, formation process, function, and potential disease-causing effects of these interactions are core questions in molecular biosciences. Recent advances in machine learning methods for solving the protein folding problem present new challenges and opportunities for the next frontiers in biomolecular science.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Shan He, Xinyue He, Lei Liu, Wenbo Zhang, Lanlan Yu, Zhun Deng, Feiyi Zhang, Mo Shanshan, Yue Fan, Zhao Xinyue, Lun Wang, Wang Chenxuan, Zhang Shuyang
Summary: Substantial controversies exist in the exploration of the molecular mechanism of heart failure, with recent research suggesting that cardiac transthyretin (TTR) amyloidosis is a major underdiagnosed cause. Investigating and modulating TTR misfolding and amyloidal aggregation can provide new insights into the molecular mechanisms of heart failure and offer novel treatment possibilities.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Allison L. Boyd, Jennifer C. Reid, Kyle R. Salci, Lili Aslostovar, Yannick D. Benoit, Zoya Shapovalova, Mio Nakanishi, Deanna P. Porras, Mohammed Almakadi, Clinton J. V. Campbell, Michael F. Jackson, Catherine A. Ross, Ronan Foley, Brian Leber, David S. Allan, Mitchell Sabloff, Anargyros Xenocostas, Tony J. Collins, Mickie Bhatia
NATURE CELL BIOLOGY
(2017)
Article
Cell & Tissue Engineering
Jong-Hee Lee, Kyle R. Salci, Jennifer C. Reid, Luca Orlando, Borko Tanasijevic, Zoya Shapovalova, Mickie Bhatia
Article
Cell & Tissue Engineering
Jennifer C. Reid, Borko Tanasijevic, Diana Golubeva, Allison L. Boyd, Deanna P. Porras, Tony J. Collins, Mickie Bhatia
Article
Oncology
Allison L. Boyd, Lili Aslostovar, Jennifer Reid, Wendy Ye, Borko Tanasijevic, Deanna P. Porras, Zoya Shapovalova, Mohammed Almakadi, Ronan Foley, Brian Leber, Anargyros Xenocostas, Mickie Bhatia
Article
Biochemistry & Molecular Biology
Mio Nakanishi, Ryan R. Mitchell, Yannick D. Benoit, Luca Orlando, Jennifer C. Reid, Kenichi Shimada, Kathryn C. Davidson, Zoya Shapovalova, Tony J. Collins, Andras Nagy, Mickie Bhatia
