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International Journal of Molecular... Jun 2017Although the copolymerizations of l-lactide (LA) with seven- or six-membered ring lactones have been extensively studied, the copolymerizations of LA with four-membered...
Although the copolymerizations of l-lactide (LA) with seven- or six-membered ring lactones have been extensively studied, the copolymerizations of LA with four-membered ring lactones have scarcely been reported. In this work, we studied the copolymerization of LA with β-propiolactone (PL) and the properties of the obtained copolymers. The copolymerization of LA with PL was carried out using trifluoromethanesulfonic acid as a catalyst and methanol as an initiator to produce poly(LA--PL) with of ~50,000 and PL-content of 6-67 mol %. The values of the copolymers were rapidly lowered with increasing PL-contents. The and Δ of the copolymers gradually decreased with increasing PL-contents, indicating their decreased crystallinity. Biodegradation test of the copolymers in compost demonstrated their improved biodegradability in comparison with the homopolymer of LA.
Topics: Biocompatible Materials; Biodegradation, Environmental; Catalysis; Dioxanes; Lactones; Materials Testing; Molecular Weight; Polymerization; Polymers; Propiolactone; Temperature
PubMed: 28632154
DOI: 10.3390/ijms18061312 -
Journal of Virology Apr 2017Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of...
Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of action remain poorly understood. Here we present cryo-electron microscopy (cryo-EM) structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids at resolutions of 3.9 Å and 6.5 Å, respectively. Notably, both particles were found to adopt an expanded conformation resembling the 135S-like uncoating intermediate, with characteristic features including an opened 2-fold channel, the externalization of the N terminus of VP1 capsid protein, and the absence of pocket factor. However, major neutralizing epitopes are very well preserved on these particles. Further biochemical analyses revealed that BPL treatment impairs the abilities of CVA16 particles to bind to the attachment receptor heparan sulfate and to a conformation-dependent monoclonal antibody in a BPL dose-dependent manner, indicating that BPL is able to modify surface-exposed amino acid residues. Taken together, our results demonstrate that BPL treatment may induce alteration of the overall structure and surface properties of a nonenveloped viral capsid, thus revealing a novel mode of action of BPL. Beta-propiolactone (BPL) is commonly used as an inactivating reagent to produce viral vaccines. It is recognized that BPL inactivates viral infectivity through modification of viral nucleic acids. However, its effect on viral proteins remains largely unknown. Here, we present high-resolution cryo-EM structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids, which reveals an expanded overall conformation and characteristic features that are typical for the 135S-like uncoating intermediate. We further show that the BPL concentration affects the binding of inactivated CVA16 particles to their receptor/antibody. Thus, BPL treatment can alter the overall structure and surface properties of viral capsids, which may lead to antigenic and immunogenic variations. Our findings provide important information for future development of BPL-inactivated vaccines.
Topics: Antibodies, Monoclonal; Antibodies, Viral; Capsid; Cryoelectron Microscopy; Disinfectants; Enterovirus; Propiolactone; Virus Inactivation
PubMed: 28148783
DOI: 10.1128/JVI.00038-17 -
Biologicals : Journal of the... Sep 1995beta-propiolactone (BPL) is an alkylating agent which reacts with many nucleophilic reagents including nucleic acids and proteins. BPL modifies the structure of nucleic...
beta-propiolactone (BPL) is an alkylating agent which reacts with many nucleophilic reagents including nucleic acids and proteins. BPL modifies the structure of nucleic acids after reaction mainly with purine residues (notably guanine). It induces nicks in DNA, cross-linking between DNA and proteins as well as between the DNA strands in the double helix. Consequently, BPL is widely used for the inactivation of viruses (DNA and RNA viruses). Moreover, it alters the capability of residual/contaminating cell DNA to be used as template by various polymerases. Thus, BPL reduces the risks associated with residual/contaminating cell DNA in biologicals.
Topics: Alkylating Agents; Animals; Cell Line; DNA; DNA, Viral; Nucleic Acid Conformation; Propiolactone; Rabies virus
PubMed: 8527119
DOI: 10.1006/biol.1995.0034 -
Virus Research Nov 2021Inactivated viral preparations are important resources in vaccine and antisera industry. Of the many vaccines that are being developed against COVID-19, inactivated...
Inactivated viral preparations are important resources in vaccine and antisera industry. Of the many vaccines that are being developed against COVID-19, inactivated whole-virus vaccines are also considered effective. β-propiolactone (BPL) is a widely used chemical inactivator of several viruses. Here, we analyze various concentrations of BPL to effectively inactivate SARS-CoV-2 and their effects on the biochemical properties of the virion particles. BPL at 1:2000 (v/v) concentrations effectively inactivated SARS-CoV-2. However, higher BPL concentrations resulted in the loss of both protein content as well as the antigenic integrity of the structural proteins. Higher concentrations also caused substantial aggregation of the virion particles possibly resulting in insufficient inactivation, and a loss in antigenic potential. We also identify that the viral RNA content in the culture supernatants can be a direct indicator of their antigenic content. Our findings may have important implications in the vaccine and antisera industry during COVID-19 pandemic.
Topics: Animals; Antigens, Viral; Antiviral Agents; COVID-19; COVID-19 Vaccines; Chlorocebus aethiops; Flocculation; Humans; Immune Sera; Propiolactone; RNA, Viral; SARS-CoV-2; Vaccines, Inactivated; Vero Cells; Virion; Virus Inactivation
PubMed: 34487766
DOI: 10.1016/j.virusres.2021.198555 -
The Journal of Biological Chemistry Oct 2011β-Propiolactone is often applied for inactivation of viruses and preparation of viral vaccines. However, the exact nature of the reactions of β-propiolactone with...
β-Propiolactone is often applied for inactivation of viruses and preparation of viral vaccines. However, the exact nature of the reactions of β-propiolactone with viral components is largely unknown. The purpose of the current study was to elucidate the chemical modifications occurring on nucleotides and amino acid residues caused by β-propiolactone. Therefore, a set of nucleobase analogues was treated with β-propiolactone, and reaction products were identified and quantified. NMR revealed at least one modification in either deoxyguanosine, deoxyadenosine, or cytidine after treatment with β-propiolactone. However, no reaction products were found from thymidine and uracil. The most reactive sides of the nucleobase analogues and nucleosides were identified by NMR. Furthermore, a series of synthetic peptides was used to determine the conversion of reactive amino acid residues by liquid chromatography-mass spectrometry. β-Propiolactone was shown to react with nine different amino acid residues. The most reactive residues are cysteine, methionine, and histidine and, to a lesser degree, aspartic acid, glutamic acid, tyrosine, lysine, serine, and threonine. Remarkably, cystine residues (disulfide groups) do not react with β-propiolactone. In addition, no reaction was observed for β-propiolactone with asparagine, glutamine, and tryptophan residues. β-Propiolactone modifies proteins to a larger extent than expected from current literature. In conclusion, the study determined the reactivity of β-propiolactone with nucleobase analogues, nucleosides, and amino acid residues and elucidated the chemical structures of the reaction products. The study provides detailed knowledge on the chemistry of β-propiolactone inactivation of viruses.
Topics: Disinfectants; Nucleosides; Peptides; Propiolactone; Viral Proteins; Virus Inactivation; Viruses
PubMed: 21868382
DOI: 10.1074/jbc.M111.279232 -
European Journal of Microbiology &... Sep 2013A reliable and complete inactivation is an indispensable premise for any concentration of rickettsiae or for the development of diagnostic strategies based on their...
A reliable and complete inactivation is an indispensable premise for any concentration of rickettsiae or for the development of diagnostic strategies based on their antigens. This study deals with the testing of methods to inactivate rickettsiae. Rickettsia honei was used as a model organism. The inactivating potency of formalin, Qiagen® antiviral lysozyme (AVL) buffer, heating to 56 °C, and β-propiolactone was analyzed in cell culture. The inactivation limits for rickettsiae were 0.1% formalin about 10 min, Qiagen AVL buffer about 5 min, 56 °C about 5 min, 0.125% β-propiolactone about 1 h, and 0.0125% β-propiolactone overnight. The interpretation was limited by cytotoxic effects of the inactivation procedures and by the culturally achievable rickettsial density in the cell culture supernatants that were used for the inactivation experiments. Reliable modes of inactivation were identified, allowing for the secure handling of rickettsial antigens for diagnostic purposes.
PubMed: 24265937
DOI: 10.1556/EuJMI.3.2013.3.6 -
Applied Microbiology Nov 1966Although beta-propiolactone (BPL) is an effective vapor-phase decontaminant for enclosed areas, some problems have been encountered in its use. Adequate air circulation...
Although beta-propiolactone (BPL) is an effective vapor-phase decontaminant for enclosed areas, some problems have been encountered in its use. Adequate air circulation during BPL dissemination could eliminate most of these problems. It is recommended that, when decontaminating the ordinary building or laboratory, the amount of BPL sprayed be changed from the previously suggested 1 gal/16,000 cubic ft of space to 1 gal/25,000 cubic ft. The use of aqueous BPL solutions and thermal-type generators is not recommended.
PubMed: 16349707
DOI: 10.1128/am.14.6.989-992.1966 -
PDA Journal of Pharmaceutical Science... 2000
Topics: Blood; Disinfectants; Propiolactone; Viral Vaccines; Viruses
PubMed: 10927912
DOI: No ID Found -
Life (Basel, Switzerland) Jan 2023This study investigates inclusion behavior of amylose towards, poly(β-propiolactone) (PPL), that is a hydrophobic polyester, via the vine-twining process in glucan...
This study investigates inclusion behavior of amylose towards, poly(β-propiolactone) (PPL), that is a hydrophobic polyester, via the vine-twining process in glucan phosphorylase (GP, isolated from thermophilic bacteria, VF5)-catalyzed enzymatic polymerization. As a result of poor dispersibility of PPL in sodium acetate buffer, the enzymatically produced amylose by GP catalysis incompletely included PPL in the buffer media under the general vine-twining polymerization conditions. Alternatively, we employed an ethyl acetate-sodium acetate buffer emulsion system with dispersing PPL as the media for vine-twining polymerization. Accordingly, the GP (from thermophilic bacteria)-catalyzed enzymatic polymerization of an α-d-glucose 1-phosphate monomer from a maltoheptaose primer was performed at 50 °C for 48 h in the prepared emulsion to efficiently form the inclusion complex. The powder X-ray diffraction profile of the precipitated product suggested that the amylose-PPL inclusion complex was mostly produced in the above system. The H NMR spectrum of the product also supported the inclusion complex structure, where a calculation based on an integrated ratio of signals indicated an almost perfect inclusion of PPL in the amylosic cavity. The prevention of crystallization of PPL in the product was suggested by IR analysis, because it was surrounded by the amylosic chains due to the inclusion complex structure.
PubMed: 36836651
DOI: 10.3390/life13020294 -
Veterinary Microbiology Nov 2018In this study, we developed and evaluated the beta-propiolactone inactivated bivalent bluetongue virus (BTV) serotypes 4 and 16 vaccine delivered with Montanide™...
Beta-propiolactone inactivated bivalent bluetongue virus vaccine containing Montanide ISA-71VG adjuvant induces long-term immune response in sheep against serotypes 4 and 16 even after 3 years of controlled vaccine storage.
In this study, we developed and evaluated the beta-propiolactone inactivated bivalent bluetongue virus (BTV) serotypes 4 and 16 vaccine delivered with Montanide™ ISA-71VG adjuvant. The safety, stability and immunological profile of the fresh and after three years of long-term storage of the vaccine formulation was analyzed. We observed after long-term storage that the vaccine emulsion was stable as indicated by unchanged pH and viscosity. The stored vaccine formulation induced virus neutralizing antibodies (VNA) in sheep against both the bluetongue virus serotypes at 7-10 day post-vaccination (dpv). VNA titers reached the peak by 60 dpv and detectable during the entire study period. Antibodies against bluetongue virus structural protein VP7 were detected by ELISA in all BTV vaccinated experimental animal groups. Partial clinical protection was observed in vaccinates against challenge virulent BTV-4 and BTV-16 serotypes by 10 dpv, while complete protection was observed at 14 dpv. The levels of viremia was decreased in challenged sheep by 10 dpv while the viremia was undetectable by 14 dpv. In summary, our newly formulated bivalent BTV (BTV-4 and BTV-16) vaccine delivered with Montanide™ ISA-71VG adjuvant was found safe and stable for over three years and induced protective response in sheep.
Topics: Adjuvants, Immunologic; Animals; Antibodies, Neutralizing; Antibodies, Viral; Bluetongue; Bluetongue virus; Drug Storage; Propiolactone; Serogroup; Sheep; Time Factors; Vaccine Potency; Vaccines, Inactivated; Viral Load; Viral Vaccines; Viremia
PubMed: 30389040
DOI: 10.1016/j.vetmic.2018.10.003