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Applied Microbiology May 1972Ionizing radiation, beta-propiolactone, and acetylethyleneimine were compared for their ability as virus-inactivating agents for the preparation of rabies vaccine. Each...
Ionizing radiation, beta-propiolactone, and acetylethyleneimine were compared for their ability as virus-inactivating agents for the preparation of rabies vaccine. Each agent reduced viral infectivity exponentially; ionizing radiation also destroyed viral hemagglutinin. The vaccine prepared by ionizing radiation was equal or superior to that prepared by beta-propiolactone in its ability to protect mice from rabies infection. The acetylethyleneimine-treated vaccine was a less potent immunogen.
Topics: Acetates; Animals; Antigens, Viral; Cell Line; Cobalt Isotopes; Complement Fixation Tests; Cricetinae; Ethylenes; Hemagglutination Tests; Hemagglutinins, Viral; Heterocyclic Compounds; Imines; Kidney; Lactones; Mice; Propionates; Rabies; Rabies Vaccines; Rabies virus; Radiation Effects; Virus Cultivation
PubMed: 5031561
DOI: 10.1128/am.23.5.914-918.1972 -
Bioorganic & Medicinal Chemistry Letters Dec 2021S-Palmitoylation is a reversible post-translational lipid modification that regulates protein trafficking and signaling. The enzymatic depalmitoylation of proteins is...
S-Palmitoylation is a reversible post-translational lipid modification that regulates protein trafficking and signaling. The enzymatic depalmitoylation of proteins is inhibited by the beta-lactones Palmostatin M and B, which have been found to target several serine hydrolases. In efforts to better understand the mechanism of action of Palmostatin M, we describe herein the synthesis, chemical proteomic analysis, and functional characterization of analogs of this compound. We identify Palmostatin M analogs that maintain inhibitory activity in N-Ras depalmitoylation assays while displaying complementary reactivity across the serine hydrolase class as measured by activity-based protein profiling. Active Palmostatin M analogs inhibit the recently characterized ABHD17 subfamily of depalmitoylating enzymes, while sparing other candidate depalmitoylases such as LYPLA1 and LYPLA2. These findings improve our understanding of the structure-activity relationship of Palmostatin M and refine the set of serine hydrolase targets relevant to the compound's effects on N-Ras palmitoylation dynamics.
Topics: Humans; Lactones; Molecular Structure; Propiolactone; Proteomics; Sulfones; ras Proteins
PubMed: 34666187
DOI: 10.1016/j.bmcl.2021.128414 -
Vox Sanguinis Jul 1969
Topics: Carcinogens; DNA; Heterocyclic Compounds; Lactones; Protein Binding; RNA
PubMed: 5798766
DOI: No ID Found -
Biologicals : Journal of the... Sep 1993Intravenous immunoglobulins and serum protein solutions are manufactured from human plasma pools of healthy, screened donors. A step-by-step validation of virus removal...
Intravenous immunoglobulins and serum protein solutions are manufactured from human plasma pools of healthy, screened donors. A step-by-step validation of virus removal and/or inactivation was performed for the manufacturing process, which includes cold ethanol fractionation, beta-propiolactone (beta-PL) treatment, UV irradiation, thermal inactivation and other chemical and physical purification steps. The total viral clearance factors achieved for the entire manufacturing process were by several magnitudes greater than the potential virus load of current plasma pools. Human immunodeficiency virus 1 (HIV-1) infectivity was reduced by > 13.4 log for 7S immunoglobulin, > 15.3 log for IGM enriched immunoglobulin and > 16 log for a 5% serum protein solution. In addition, high clearance rate for a broad spectrum of model viruses was demonstrated for all three blood derivatives being > 23.2 to > 27.8 log for pseudo rabies virus (PSR), > 12.3 to > 22.6 log for vesicular stomatitis virus (VSV) and 6.9-10.6 log for simian virus 40 (SV40). For the beta-propiolactone inactivation step Hepatitis C model viruses, e.g. equine arteritis virus (EAV) and bovine viral diarrhoea virus (BVDV) were also investigated.
Topics: Blood; Blood Proteins; Cells, Cultured; Cold Temperature; Drug Contamination; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Propiolactone; Viruses
PubMed: 8117439
DOI: 10.1006/biol.1993.1083 -
Journal of Biological Standardization Apr 1976
Topics: Acholeplasma laidlawii; Animals; Cell Line; Dogs; Drug Contamination; Formaldehyde; Haplorhini; Kidney; Lactones; Mycoplasma; Phenols; Propiolactone; Time Factors; Vaccines
PubMed: 819443
DOI: 10.1016/0092-1157(76)90026-3 -
Archives of Surgery (Chicago, Ill. :... Apr 1964
Topics: Anti-Infective Agents; Anti-Infective Agents, Local; Blood Preservation; Blood Transfusion; Hepatitis; Hepatitis B virus; Humans; Lactones; Preventive Medicine; Propiolactone; Sterilization; Ultraviolet Rays
PubMed: 14107028
DOI: 10.1001/archsurg.1964.01310220211032 -
Langmuir : the ACS Journal of Surfaces... Nov 2011The production protocol of many whole cell/virion vaccines involves an inactivation step with β-propiolactone (BPL). Despite the widespread use of BPL, its mechanism of...
Effect of the β-propiolactone treatment on the adsorption and fusion of influenza A/Brisbane/59/2007 and A/New Caledonia/20/1999 virus H1N1 on a dimyristoylphosphatidylcholine/ganglioside GM3 mixed phospholipids monolayer at the air-water interface.
The production protocol of many whole cell/virion vaccines involves an inactivation step with β-propiolactone (BPL). Despite the widespread use of BPL, its mechanism of action is poorly understood. Earlier work demonstrated that BPL alkylates nucleotide bases, but its interaction with proteins has not been studied in depth. In the present study we use ellipsometry to analyze the influence of BPL treatment of two H1N1 influenza strains, A/Brisbane/59/2007 and A/New Caledonia/20/1999, which are used for vaccine production on an industrial scale. Analyses were conducted using a mixed lipid monolayer containing ganglioside GM3, which functions as the viral receptor. Our results show that BPL treatment of both strains reduces viral affinity for the mixed monolayer and also diminishes the capacity of viral domains to self-assemble. In another series of experiments, the pH of the subphase was reduced from 7.4 to 5 to provoke the pH-induced conformational change of hemagglutinin, which occurs following endocytosis into the endosome. In the presence of the native virus the pH decrease caused a reduction in domain size, whereas lipid layer thickness and surface pressure were increased. These observations are consistent with a fusion of the viral membrane with the lipid monolayer. Importantly, this fusion was not observed with adsorbed inactivated virus, which indicates that BPL treatment inhibits the first step of virus-membrane fusion. Our data also indicate that BPL chemically modifies hemagglutinin, which mediates the interaction with GM3.
Topics: Adsorption; Air; Dimyristoylphosphatidylcholine; Endocytosis; G(M3) Ganglioside; Hydrogen-Ion Concentration; Influenza A Virus, H1N1 Subtype; Propiolactone; Water
PubMed: 21981550
DOI: 10.1021/la2027175 -
Vaccine Feb 2016Development of safe and protective vaccines against infectious pathogens remains a challenge. Inactivation of rabies virus is a critical step in the production of...
Development of safe and protective vaccines against infectious pathogens remains a challenge. Inactivation of rabies virus is a critical step in the production of vaccines and other research reagents. Beta-propiolactone (βPL); the currently used inactivating agent for rabies virus is expensive and proved to be carcinogenic in animals. This study aimed to investigate the ability of hydrogen peroxide (H2O2) to irreversibly inactivate rabies virus without affecting its antigenicity and immunogenicity in pursuit of finding safe, effective and inexpensive alternative inactivating agents. H2O2 3% rapidly inactivated a Vero cell adapted fixed rabies virus strain designated as FRV/K within 2h of exposure without affecting its antigenicity or immunogenicity. No residual infectious virus was detected and the H2O2-inactivated vaccine proved to be safe and effective when compared with the same virus harvest inactivated with the classical inactivating agent βPL. Mice immunized with H2O2-inactivated rabies virus produced sufficient level of antibodies and were protected when challenged with lethal CVS virus. These findings reinforce the idea that H2O2 can replace βPL as inactivating agent for rabies virus to reduce time and cost of inactivation process.
Topics: Animals; Antibodies, Viral; Chlorocebus aethiops; Guinea Pigs; Hydrogen Peroxide; Mice; Propiolactone; Rabies; Rabies Vaccines; Rabies virus; Vaccines, Inactivated; Vero Cells; Virus Inactivation
PubMed: 26731189
DOI: 10.1016/j.vaccine.2015.12.041 -
Emerging Infectious Diseases Aug 2005
Topics: Adjuvants, Immunologic; Animals; Antibodies, Viral; Immunization; Mice; Mice, Inbred BALB C; Propiolactone; Severe acute respiratory syndrome-related coronavirus; Severe Acute Respiratory Syndrome; Vaccines, Attenuated; Vaccines, DNA; Viral Vaccines; Virus Replication
PubMed: 16110580
DOI: 10.3201/eid1108.041003 -
Lancet (London, England) May 1985
Topics: Acquired Immunodeficiency Syndrome; Blood Chemical Analysis; Disinfection; Humans; Lactones; Propiolactone; Specimen Handling; Sterilization
PubMed: 2860363
DOI: 10.1016/s0140-6736(85)92465-1