Phenyl-n-butylborinic acid is a potent transition state analog inhibitor of lipolytic enzymes

Sutton, Larry D.; Stout, Jay S.; Hosie, L; Spencer, Patricia S.; Quinn, Daniel M.

doi:10.1016/0006-291x(86)90575-9

Cited by 44 publications

(19 citation statements)

References 18 publications

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“…Three boronic acids were tested as urease inhibitors, and each was shown to exhibit competitive inhibition ( Table 2). Boronic acids have been investigated by others as competitive inhibitors in a variety of serine hydrolases, including chymotrypsin [14][15][16], subtilisin [16,17], acetylcholinesterase [18], pig pancreatic lipase [19], elastase [20], cathepsin G [20], cholesterol esterase [21] and lipoprotein lipase [21]. Two examples, subtilisin and chymotrypsin, were examined by crystallographic methods [22,23]; inhibitory boronic acids were shown to be bound to the active-site serine residue, apparently isosteric with the substrate transition state.…”

Section: Boric Acid Inhibitionmentioning

confidence: 99%

Proteus mirabilis urease. Partial purification and inhibition by boric acid and boronic acids

Breitenbach

Hausinger

1988

Biochemical Journal

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Urease was purified 800-fold and partially characterized from Proteus mirabilis, the predominant microorganism associated with urinary stones. Boric acid is a rapid reversible competitive inhibitor of urease. The pH-dependence of inhibition exhibited pKa values of 6.25 and 9.3, where the latter value is probably due to the inherent pKa of boric acid. Three boronic acids also were shown to inhibit urease competitively.

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Section: Boric Acid Inhibitionmentioning

confidence: 99%

Proteus mirabilis urease. Partial purification and inhibition by boric acid and boronic acids

Breitenbach

Hausinger

1988

Biochemical Journal

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“…Among the naphthalene derivatives, the introduction of an acidic group, such as a sulfonylic group, was attempted in order to improve solubility in water, but only compound 11 was obtained. Unfortunately, the activity of compound 11 was about ten times lower than that of the other naphthalene derivatives (12)(13)(14). By combining the phenol and the naphthol moieties that proved to be the best (compounds 12 and 14), compounds 15a and 16a were obtained.…”

Section: Biological Results and Discussionmentioning

confidence: 96%

“…These molecules act as transition state analogues competing with the b-lactam antibiotic and deactivating the enzyme. [11][12][13][14][15] Virtual screening of the commercially available boronic acid derivatives, using the DOCK 3.5 DO CK 3.5 program, led to the identification of 3-amino-phenyl-boronic acid (1, Fig. 1), which shows a K i of 7.3 lM against Escherichia coli AmpC-b-lactamase (bL).…”

Section: Introductionmentioning

confidence: 99%

Aza-boronic acids as non-β-lactam inhibitors of AmpC-β-lactamase

Buzzoni

Blázquez

Ferrari

et al. 2004

Bioorganic & Medicinal Chemistry Letters

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“…Studies of CE binding have supported the hypothesis that the active site of CE is composed of two binding regions, one that binds to the large, hydrophobic rings and the other that binds to the hydrocarbon chains of the fatty acid. 43,44 The specificity of the latter region for straight, aliphatic hydrocarbon chains was determined by using a series of CE inhibitors. 44 A number of n-alkylboronic acid inhibitors, ranging from one to eight carbons, were shown to inhibit the hydrolysis of p-nitrophenylbuyrate.…”

Section: Discussionmentioning

confidence: 99%

Biological characterization of a novel biodegradable antimicrobial polymer synthesized with fluoroquinolones

Woo¹,

Yang²,

Yin³

et al. 2001

J. Biomed. Mater. Res.

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Biomaterial-related infections continue to represent a significant challenge to the medical community. Several approaches have been utilized to incorporate antimicrobial agents at the surface of implant devices in attempts to delay or eliminate the formation of biofilms. To date, most of these strategies have focused on drug conjugation or diffusion-limited systems for the delivery of such pharmaceutical agents. More recently, work has been presented on the feasibility of incorporating drugs into the backbone of polymers as a main-chain monomer. When sequenced into the backbone of the polymer with other monomers that are hydrolytically sensitive to enzyme-catalyzed breakdown, it is thought that drugs may be able to be selectively released. Specifically, degradable polyurethanes have been synthesized with fluoroquinolone antibiotics and have shown an ability to kill bacteria when released following degradation of the polymer chains by the macrophage-derived enzyme cholesterol esterase. However, specificity of the cleavage sites in the polymer was difficult to control. Since cholesterol esterase has specificity for hydrophobic moieties, it is desirable to alter the formulation of the polyurethanes to incorporate long hydrophobic monomers immediately adjacent to the ciprofloxacin molecule. Hence, the current study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 diisocyanatohexane, which was used in previous work. Validation of specific ciprofloxacin release and the generation of antimicrobial are shown. A preliminary cell study to assess the cytotoxicity of this biodegradable antibiotic polymer shows that the material has no observable effects on cell proliferation or cell membrane structure.

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Phenyl-n-butylborinic acid is a potent transition state analog inhibitor of lipolytic enzymes

Cited by 44 publications

References 18 publications

Proteus mirabilis urease. Partial purification and inhibition by boric acid and boronic acids

Proteus mirabilis urease. Partial purification and inhibition by boric acid and boronic acids

Aza-boronic acids as non-β-lactam inhibitors of AmpC-β-lactamase

Biological characterization of a novel biodegradable antimicrobial polymer synthesized with fluoroquinolones

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