Carcinogenesis of β-Propiolactone: A Computational Study

Španinger, Eva; Bren, Urban

doi:10.1021/acs.chemrestox.9b00389

Cited by 15 publications

(16 citation statements)

References 43 publications

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“…Polymers or copolymers-based lactones are used in many sectors of the industry; however, not all of them can be successfully used considering the toxicity, e.g., β-propiolactonebased products. [36]. As mentioned earlier, polymers based on lactones can be used in medicine as bioresorbable materials.…”

Section: Products Produced From Lactones and Their Applicationsmentioning

confidence: 95%

“…Table 1 lists the initiators or catalysts used in some of the polymer/copolymer preparation methods based on the known lactones. Tin octanoate (SnOct 2 )/1,4-benzenedimethanol (BDM) [62] mPEG Poly(mEG-co-ε-DL) mPEG [63] As mentioned in the previous section, the interest in research and the possibilities of using polymers and copolymers of β-propiolactone have decreased in recent years due to its potential carcinogenic properties [36]. As a result, these compounds were practically excluded from use, both in the biomedical industry, as well as in products that have long-term contact with humans.…”

Section: Methods For the Synthesis Of Lactones Derivativesmentioning

confidence: 99%

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Recent Developments in Lactone Monomers and Polymer Synthesis and Application

2021

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Lactones are a group of compounds that have been known for several decades. The commercial importance of lactones results from the possibility of manufacturing of a broad scope of derivatives and polymers with a wide spectrum of applications. In this work the synthesis and characterization of simple lactones are described, which due to the easy methods of the synthesis are of high importance for the industry. The chemical as well as biochemical methods are included with special attention paid to the methods that avoid metal catalysts, initiators or toxic solvents, allowing the use of the final products for the medical applications, e.g., for controlled drug-release systems, resorbable surgical threads, implants, tissue scaffolds or for the production of drugs. Lactone-based derivatives, such as polymers, copolymers, composites or three-dimensional structures are also presented. The work is focused on the methods for the synthesis of lactones and lactones derivates, as well as on the special properties and application of the studied compounds.

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Section: Products Produced From Lactones and Their Applicationsmentioning

confidence: 95%

Section: Methods For the Synthesis Of Lactones Derivativesmentioning

confidence: 99%

Recent Developments in Lactone Monomers and Polymer Synthesis and Application

2021

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“…Glycerol [ 45 ], β-alanine [ 46 ], and exogenously supplemented 3HP are used as precursors of 3HP units. The use of nontoxic starting substances is a benefit of P(3HP) biosynthesis compared to ROP of β-propiolactone [ 47 ] with a carcinogenic effect [ 48 ]. P(3HP) has high tensile strength and stretchable properties, and it is degraded by PHA depolymerase activity [ 44 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

Versatile aliphatic polyester biosynthesis system for producing random and block copolymers composed of 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates using the sequence-regulating polyhydroxyalkanoate synthase PhaCAR

et al. 2022

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Background Polyhydroxyalkanoates (PHAs) are microbial polyesters synthesized by PHA synthases. Naturally occurring PHA copolymers possess a random monomer sequence. The development of PhaCAR, a unique sequence-regulating PHA synthase, has enabled the spontaneous biosynthesis of PHA block copolymers. PhaCAR synthesizes both a block copolymer poly(2-hydroxybutyrate)-b-poly(3-hydroxybutyrate) [P(2HB)-b-P(3HB)], and a random copolymer, poly(3HB-co-3-hydroxyhexanoate), indicating that the combination of monomers determines the monomer sequence. Therefore, in this study, we explored the substrate scope of PhaCAR and the monomer sequences of the resulting copolymers to identify the determinants of the monomer sequence. PhaCAR is a class I PHA synthase that is thought to incorporate long-main-chain hydroxyalkanoates (LMC HAs, > C3 in the main [backbone] chain). Thus, the LMC monomers, 4-hydroxy-2-methylbutyrate (4H2MB), 5-hydroxyvalerate (5HV), and 6-hydroxyhexanoate (6HHx), as well as 2HB, 3HB, and 3-hydroxypropionate (3HP) were tested. Results Recombinant Escherichia coli harboring PhaCAR, CoA transferase and CoA ligase genes was used for PHA production. The medium contained the monomer precursors, 2HB, 3HB, 3HP, 4H2MB, 5HV, and 6HHx, either individually or in combination. As a result, homopolymers were obtained only for 3HB and 3HP. Moreover, 3HB and 3HP were randomly copolymerized by PhaCAR. 3HB-based binary copolymers P(3HB-co-LMC HA)s containing up to 2.9 mol% 4H2MB, 4.8 mol% 5HV, or 1.8 mol% 6HHx were produced. Differential scanning calorimetry analysis of the copolymers indicated that P(3HB-co-LMC HA)s had a random sequence. In contrast, combining 3HP and 2HB induced the synthesis of P(3HP)-b-P(2HB). Similarly, P(2HB) segment-containing block copolymers P(3HB-co-LMC HA)-b-P(2HB)s were synthesized. Binary copolymers of LMC HAs and 2HB were not obtained, indicating that the 3HB or 3HP unit is essential to the polymer synthesis. Conclusion PhaCAR possesses a wide substrate scope towards 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates. 3HB or 3HP units are essential for polymer synthesis using PhaCAR. The presence of a 2HB monomer is key to synthesizing block copolymers, such as P(3HP)-b-P(2HB) and P(3HB-co-LMC HA)-b-P(2HB)s. The copolymers that did not contain 2HB units had a random sequence. This study’s results provide insights into the mechanism of sequence regulation by PhaCAR and pave the way for designing PHA block copolymers.

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“…Recently, two groups have developed whole-virus-inactivated SARS-CoV-2 vaccines using β-propiolactone, and evaluated their efficacy and immunogenicity in nonhuman primates [7,8]. β-propiolactone or formalin, commonly used compounds to inactivate viruses, are potentially carcinogenic compounds that inactivate viruses at the protein and nucleic acid levels [9,10].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice

et al. 2021

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The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there are only three whole-virus vaccine candidates produced using β-propiolactone or formalin inactivation. Here, we prepared a whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) using a novel psoralen inactivation method and evaluated its immunogenicity in mice using two different adjuvants, alum and Advax-2. We compared the immunogenicity of SARS-CoV-2 PsIV against SARS-CoV-2 DNA vaccines expressing either full-length or truncated spike proteins. We also compared the psoralen-inactivated vaccine against a DNA prime, psoralen-inactivated vaccine boost regimen. After two doses, the psoralen-inactivated vaccine, when administered with alum or Advax-2 adjuvants, generated a dose-dependent neutralizing antibody responses in mice. Overall, the pattern of cytokine ELISPOT responses to antigen-stimulation observed in this study indicates that SARS-CoV-2 PsIV with the alum adjuvant promotes a Th2-type response, while SARS-CoV-2 PsIV with the Advax-2 adjuvant promotes a Th1-type response.

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Carcinogenesis of β-Propiolactone: A Computational Study

Cited by 15 publications

References 43 publications

Recent Developments in Lactone Monomers and Polymer Synthesis and Application

Recent Developments in Lactone Monomers and Polymer Synthesis and Application

Versatile aliphatic polyester biosynthesis system for producing random and block copolymers composed of 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates using the sequence-regulating polyhydroxyalkanoate synthase PhaCAR

Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice

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