Photoreactivity of lysergic acid diethylamide and its possible utility as a photoaffinity labeling reagent

Walker, Edward B.; McNall, Steven J.; Mansour, Tag E.

doi:10.1016/0006-2952(83)90279-4

Cited by 13 publications

(2 citation statements)

References 22 publications

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“…They exhibit broad and overlapping substrate specificity toward esters and amides, and the same substrate is often hydrolyzed by more than one enzyme. Consequently, their classification is difficult and still is in a somewhat confused state, despite the important roles that carboxylesterase (EC 3.1.1.1) and/or other carboxylic ester hydrolases, such as arylesterase (EC 3.1.1.2) and cholinesterase (EC 3.1.1.8), play in the metabolism of many xenobiotics. − Humans have been shown to express carboxylesterase in the liver, plasma, small intestine, brain, stomach, colon, macrophage, and monocytes …”

Section: Introductionmentioning

confidence: 99%

“…Esterase activity varies quite strongly between species. − The stability of acyloxyalkyl type esters, most frequently employed in prodrug and soft drug designs, usually increases in the rat < rabbit < dog < human order, , but there might be considerable variability. Rodents (rats, guinea pigs) tend to metabolize ester-containing drugs much faster than humans.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Structure−Metabolism Relationships: Steric and Nonsteric Effects in the Enzymatic Hydrolysis of Noncongener Carboxylic Esters

Buchwald

Bodor

1999

J. Med. Chem.

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An attempt to quantitatively describe human blood in vitro hydrolysis data for more than 80 compounds belonging to seven different noncongener series of ester-containing drugs is presented. A parameter not yet explored in pharmaceutical studies, the inaccessible solid angle Omega(h), calculated around different atoms was used as a measure of steric hindrance, and the steric hindrance around the carbonyl sp(2) oxygen (Omega(h)(O=)) proved the most relevant parameter. The obtained final equation, log t(1/2) = -3.805 + 0.172Omega(h)(O=) - 10.146q(C=) + 0.112QLogP, also includes the AM1-calculated charge on the carbonyl carbon (q(C=)) and a calculated log octanol-water partition coefficient (QLogP) as parameters and accounts for 80% of the variability in the log half-lives of 67 compounds. A number of structures are still mispredicted, but the equation agrees very well with a recently proposed mechanism for hydrolysis by carboxylesterases. The model, with a predictive power tested here on three unrelated structures, should be useful in estimating approximate rates of hydrolysis for prodrug or soft drug candidates ahead of their synthesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative Structure−Metabolism Relationships: Steric and Nonsteric Effects in the Enzymatic Hydrolysis of Noncongener Carboxylic Esters

Buchwald

Bodor

1999

J. Med. Chem.

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Biochemistry and Pharmacology of the 5-HT1 Serotonin Binding Sites

Nelson¹

1988

The Serotonin Receptors

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Esterase isozymes in a solitary bee,Megachile rotundata (fab.): Characterization, developmental multiplicity, and adult variability

et al. 1990

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This study describes the biochemical characterization and genetic variation of cytosolic esterases in the alfalfa leafcutting bee, Megachile rotundata (Fab.). Esterase isozymes were separated by nondenaturing polyacrylamide gel electrophoresis and isoelectric focusing and characterized by inhibition with eserine sulfate, EDTA, paraoxon, and p-hydroxymercuribenzoate. Based on inhibition patterns and substrate specificity, there are major differences between adults and immature forms and more subtle differences between male and female adults. M. rotundata esterases are largely organophosphate sensitive and the two major adult allozymes were highly variable within the population examined. Differences in esterase expression between life stages with respect to niche and the occurrence of diploid males are discussed.

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Photoreactivity of lysergic acid diethylamide and its possible utility as a photoaffinity labeling reagent

Cited by 13 publications

References 22 publications

Quantitative Structure−Metabolism Relationships: Steric and Nonsteric Effects in the Enzymatic Hydrolysis of Noncongener Carboxylic Esters

Quantitative Structure−Metabolism Relationships: Steric and Nonsteric Effects in the Enzymatic Hydrolysis of Noncongener Carboxylic Esters

Biochemistry and Pharmacology of the 5-HT1 Serotonin Binding Sites

Esterase isozymes in a solitary bee,Megachile rotundata (fab.): Characterization, developmental multiplicity, and adult variability

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