Butyrylcholinesterase activity towards long-chain alkanoylcholines: kinetics and mechanism

Chelminska-Bertilsson, Monika; Allenmark, Stig; Edebo, L.

doi:10.1016/0167-4838(93)90062-v

Cited by 15 publications

(10 citation statements)

References 10 publications

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“…Early studies of BChE indicated that butyrylcholine is the substrate with optimal activity and that long-chain alkanoylcholines are not hydrolyzed by the enzyme (9). We found, however, that the long-chain alkanoylcholines are hydrolyzed in vitro but that the reaction does not follow Michaelis-Menten kinetics and shows deviation from linearity caused by inhibition of the reaction at high substrate concentrations (4). We showed that the inhibition could be a result of conformational changes of the protein due to the amphiphilic nature of the substrates.…”

mentioning

confidence: 75%

“…However, since the antimicrobial effect is dependent to a large extent on the number of carbon atoms in the hydrophobic chain, substances with similar chain lengths should be compared. The motivation for comparing C 14 with CTAB (CTAB has 16 carbon atoms in the hydrophobic chain) is that for both the betaine and choline esters the critical micelle concentration is similar to that of a stable quarternary ammonium compound with two extra CH 2 groups, i.e., the critical micelle concentration of C 14 is comparable to that of CTAB (4,17). This would indicate that the ester function will be infused into the hydrophobic interior of the micelle.…”

Section: Discussionmentioning

confidence: 99%

“…The solution was then extracted twice with diethyl ether, and the organic phase was dried with MgSO 4 . An appropriate amount of [ 3 H]methyl iodide dissolved in toluene was added, and the solution, in a thoroughly closed vial, was left for 2 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…1) (4). Our interest in these compounds was due to their potential degradation by hydrolytic enzymes.…”

mentioning

confidence: 99%

“…Thus, for the alkanoylcholines a more appropriate comparison might have been CTAB and a C 16 ester. However, for the alkanoylcholines, we have only tested chain lengths of up to 14 carbon atoms because of the negative effect on enzymatic hydrolysis by the more hydrophobic esters (4). Tetradecanoylcholine, C 14 , being the most effective ester, was chosen as the test substance against a representative selection of different bacteria and yeasts ( Table 1).…”

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confidence: 99%

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Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable

Ahlström

Chelminska-Bertilsson

Thompson

et al. 1995

Antimicrob Agents Chemother

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A new category of amphiphilic hydrolyzable quaternary ammonium compounds with rapid and high levels of antimicrobial activity was studied. The compounds, alkanoylcholines with hydrocarbon chains of 10 to 14 carbon atoms, are hydrolyzed by butyrylcholine esterase, which is present in human serum and mucosal membranes. The hydrolysis products are common components of human metabolism. Alkanoylcholines were tested and found to be active against gram-negative and gram-positive bacteria as well as yeasts. The microbicidal activities of the alkanoylcholines were comparable to the activities of the stable quaternary ammonium compounds of corresponding chain length and increased with an increasing number of carbon atoms. The compounds were also found to be hydrolyzed by enzymes present in certain microorganisms. The degradation was achieved after reaching the microbicidal effect.

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mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…1) (4). Our interest in these compounds was due to their potential degradation by hydrolytic enzymes.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable

Ahlström

Chelminska-Bertilsson

Thompson

et al. 1995

Antimicrob Agents Chemother

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Soft Drugs

Bodor

Buchwald

2012

Retrometabolic Drug Design and Targeting

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Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients

Jörgensen

Wibel

Bernkop‐Schnürch

2023

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The use of cationic and ionizable cationic lipids in pharmaceutical products, however, is a double-edged sword, as these excipients are of considerable safety concerns. Because of their permanent or pHdependent cationic nature, they perturbate cellular and nuclear membranes, trigger the release of degrading enzymes from lysosomes, cause mitochondrial permeabilization and dysfunction, generate reactive oxygen species (ROS), alter cytoplasmatic enzyme functions, and damage DNA. [3] To address this substantial shortcoming of cationic and ionizable cationic lipids, biodegradable alternatives have been introduced that are rapidly degraded in vivo to preferably endogenous metabolites. The design of such lipids is inspired by natural cationic or ionizable cationic compounds like arginine, lysine or betaine that are generally regarded as safe. Their conjugation to endogenous lipids like fatty acids or cholesterol results in amphiphilic lipids. As ester and amide bonds are cleaved in vivo by numerous enzymes such as lipases, esterases, and proteases, they are the preferred linkages between these natural building blocks.Since the FDA approved ethyl Nα-lauroyl-l-arginate as biodegradable food preservative being effective against a broad range of Gram-positive and Gram-negative bacteria, yeasts, and molds in 2005, [4] the potential use of biodegradable cationic and ionizable cationic lipids as pharmaceutical excipients has been evaluated by numerous research groups. As these excipients exhibit the same properties as their non-biodegradable counterparts but causing relatively low adverse effects, they will likely substitute currently used non-biodegradable lipids in the future. Within this review, we provide an overview on the different types of biodegradable cationic and ionizable cationic lipids, their synthesis and cleavage by endogenous enzymes. Applications in drug delivery systems and as antimicrobial agents are discussed. A guideline on their design and application is provided and an outlook on future developments is given. Building Blocks and Formation of Cationic and Ionizable Cationic LipidsGenerally, biodegradable cationic and ionizable cationic lipids are composed of biocompatible building blocks that are conjugated via a linkage such as an ester or amide bond. [5] Representative building blocks and linkages are depicted in Figure 1. Endogenous enzymes can break these linkages and degrade Cationic and ionizable cationic lipids are broadly applied as auxiliary agents, but their use is associated with adverse effects. If these excipients are rapidly degraded to endogenously occurring metabolites such as amino acids and fatty acids, their toxic potential can be minimized. So far, synthesized and evaluated biodegradable cationic and ionizable cationic lipids already showed promising results in terms of functionality and safety. Within this review, an overview about the different types of such biodegradable lipids, the available building blocks, their synthesis and cleavage by endogenous enzymes is provided. Moreover, ...

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Butyrylcholinesterase activity towards long-chain alkanoylcholines: kinetics and mechanism

Cited by 15 publications

References 10 publications

Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable

Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable

Soft Drugs

Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients

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