Synthesis and Enzymatic Hydrolysis of Esters, Constituting Simple Models of Soft Drugs.

Graffner-Nordberg, Malin; Sjödin, Karin; Tunek, Anders; Hallberg, Anders

doi:10.1248/cpb.46.591

Cited by 47 publications

(74 citation statements)

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“…In rabbits, microsomal carboxylesterases are shown to interact with and regulate the secretion of acute-phase response proteins, such as C-reactive protein (Macintyre et al, 1994). Given the fact that many therapeutic agents are esters or amides, carboxylesterase-mediated hydrolysis is given an important consideration in drug designs (Graffner-Nordberg et al, 1998;Buchwald and Bodor, 1999).…”

mentioning

confidence: 99%

Human and Rodent Carboxylesterases: Immunorelatedness, Overlapping Substrate Specificity, Differential Sensitivity to Serine Enzyme Inhibitors, and Tumor-Related Expression

Xie¹,

Yang²,

Liu³

et al. 2002

Drug Metab Dispos

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ABSTRACT:Carboxylesterases hydrolyze numerous endogenous and foreign compounds with diverse structures. Humans and rodents express multiple forms of carboxylesterases, which share a high degree of sequence identity (ϳ70%). Alignment analyses locate in carboxylesterases several functional subsites such the catalytic triad as seen in acetylcholinesterase. The aim of this study was to determine among human and rodent carboxylesterases the immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, tissue distribution, and tumor-related expression. Six antibodies against whole carboxylesterases or synthetic peptides were tested for their reactivity toward 11 human or rodent recombinant carboxylesterases. The antibodies against whole proteins generally exhibited a broader cross-reactivity than the anti-peptide antibodies. All carboxylesterases hydrolyzed para-nitrophenylacetate and para-nitrophenylbutyrate. However, the relative activity varied markedly from enzyme to enzyme (>20-fold), and some carboxylesterases showed a clear substrate preference. Carboxylesterases with the same functional subsites had a similar profile on substrate specificity and sensitivity toward phenylmethylsulfonyl fluoride (PMSF) and paraoxon, suggesting that these subsites play determinant roles in the recognition of substrates and inhibitors. Among three human carboxylesterases, HCE-1 hydrolyzed both substrates to a similar extent, whereas HCE-2 and HCE-3 showed an opposite substrate preference. All three enzymes were inhibited by PMSF and paraoxon, but they showed a marked difference in relative sensitivities. Based on immunoblotting analyses, HCE-1 was present in all tissues examined, whereas HCE-2 and HCE-3 were expressed in a tissue-restricted pattern. Colon carcinomas expressed slightly higher levels of HCE-1 and HCE-2 than the adjacent normal tissues, whereas the opposite was true with HCE-3.

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mentioning

confidence: 99%

Human and Rodent Carboxylesterases: Immunorelatedness, Overlapping Substrate Specificity, Differential Sensitivity to Serine Enzyme Inhibitors, and Tumor-Related Expression

Xie¹,

Yang²,

Liu³

et al. 2002

Drug Metab Dispos

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“…In biomedical-related research, interaction with viruses should be considered and a switchable process introducing a trigger with a specific enzyme [119] or metal complexes as mimics [120] would be beneficial as a sophisticated nanosystem for delivery.…”

Section: Conclusion and Outcomementioning

confidence: 99%

Switchable Materials Containing Polyzwitterion Moieties

2015

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Abstract:In recent decades, the design and construction of smart materials capable of switching into a polyzwitterionic state by an external trigger have been intensively pursued. Polyzwitterionic states have unique antifouling and surface properties and external triggers, such as pH, light, ions, electric field and CO 2 , cause significant changes in materials with regard to overall charge, ionic strength and wettability. This survey highlights current progress in the irreversible as well as the reversible switching process involving polyzwitterionic moieties, which can, in turn, be applied to studying the interaction of various interfaces with biological species as protein, DNA, bacteria or platelets and also for advanced use.

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“…Carboxylesterases are found in the endoplasmic reticulum of most mammalian tissues; however, they are most abundant in hepatocytes (Anders, 1989;Graffner-Nordberg et al, 1998;Hosokawa et al, 2001). …”

Section: Iii1 Hydrolysismentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 30, Revision 1 (FGE.30Rev1): 4‐Prop‐1‐enylphenol and 2‐methoxy‐4‐(prop‐1‐enyl)phenyl 3‐methylbutyrate from chemical group 17

Flavourings¹

2011

EFS2

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate two flavouring substances in the Flavouring Group Evaluation 30, Revision 1, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances were considered to have genotoxic potential. The two substances were evaluated through a stepwise approach that integrates information on structure‐activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the two substances [FL‐no: 04.097, 09.894] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. For [FL‐no: 09.894] the composition of the stereoisomeric mixture needs to been specified.

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Synthesis and Enzymatic Hydrolysis of Esters, Constituting Simple Models of Soft Drugs.

Cited by 47 publications

References 1 publication

Human and Rodent Carboxylesterases: Immunorelatedness, Overlapping Substrate Specificity, Differential Sensitivity to Serine Enzyme Inhibitors, and Tumor-Related Expression

Human and Rodent Carboxylesterases: Immunorelatedness, Overlapping Substrate Specificity, Differential Sensitivity to Serine Enzyme Inhibitors, and Tumor-Related Expression

Switchable Materials Containing Polyzwitterion Moieties

Scientific Opinion on Flavouring Group Evaluation 30, Revision 1 (FGE.30Rev1): 4‐Prop‐1‐enylphenol and 2‐methoxy‐4‐(prop‐1‐enyl)phenyl 3‐methylbutyrate from chemical group 17

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