PubMed Health⌕ Search

Biomedical subjects

F H Westheimer

Publications and source records attributed to F H Westheimer.

At least 19 recordsLinked to original sources
PubMed2003

Musings.

Explore the source record for details and available documents.

Biochemistry↗
PubMed1987

Why nature chose phosphates.

Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the diesters against hydrolysis and to retain the molecules within a lipid membrane. A similar explanation for stability and retention also holds for phosphates that are intermediary metabolites and for phosphates that serve as energy sources. Phosphates with multiple negative charges can react by way of the monomeric metaphosphate ion PO3- as an intermediate. No other residue appears to fulfill the multiple roles of phosphate in biochemistry. Stable, negatively charged phosphates react under catalysis by enzymes; organic chemists, who can only rarely use enzymatic catalysis for their reactions, need more highly reactive intermediates than phosphates.

Amides↗
PubMed1980

Inhibition of orotidine-5'-phosphate decarboxylase by 1-(5'-phospho-beta-d-ribofuranosyl)barbituric acid, 6-azauridine 5'-phosphate, and uridine 5'-phosphate.

1-(5'-Phospho-beta-D-ribofuranosyl)barbituric acid, an analogue of orotidylic acid, binds to orotidine-5'-phosphate decarboxylase about 100000 times as strongly as does the substrate. The Ki at pH 6 is 9 X 10(-12) M and the half-time for dissociation at 4 degrees C is about 10 h. The binding of the barbiturate analogue to the enzyme is thus one of the strongest interactions between small molecules and proteins that have been measured. The possibility that the inhibitor is a transition-state analogue is discussed.

Carboxy-Lyases↗
PubMed1979

The purification of orotidine-5'-phosphate decarboxylase from yeast by affinity chromatography.

We have prepared an affinity column for the purification of orotidine-5'-phosphate decarboxylase from yeast. The column effects a 3200-fold purification from yeast homogenate in one pass; simple additional steps produce enzyme that has been purified 6700-fold and is not contaminated by any other protein that can be detected by sodium dodecyl sulfate-acrylamide gel electrophoresis. Overall, 35% of the activity present in the yeast is recovered as pure enzyme. The resin for the column is synthesized by attaching the ethylenediamine amide of 5-(2-carboxyethyl)-6-azauridine 5'-phosphate to carboxymethyl-agarose.

Carboxy-Lyases↗
PubMed1976

2-diazo-3,3,3-trifluoropropionyl chloride: reagent for photoaffinity labeling.

2-Diazo-3,3,3-trifluoropropionyl chloride has been synthesized from trifluorodiazoethane and phosgene. Its derivatives are acid stable, can be used to label enzymes, and undergo photolysis with substantially less rearrangement than do derivatives of other known diazoacyl reagents designed for photoaffinity labeling. In particular, the diazotrifluoropropionyl thioester of methyl N-acetylcysteine undergoes photolysis in methanol with about 40% insertion into the - OH bond of the solvent; by contrast, photolysis of other diazoacyl thioesters gives substantially quantitative Wolff rearrangement. The trifluoro compounds hold promise for the photoaffinity labeling of thiols.

Affinity Labels↗
PubMed1975

The enthalpies of hydrolysis of acyclic, monocyclic, and glycoside cyclic phosphate diesters.

The enthalpies of hydrolysis of acyclic, monocyclic, and glycoside cyclic phosphate diesters have been measured by flow microcalorimetry using a phosphohydrolase isolated from Enterobacter aerogenes as catalyst. The values so obtained (kilocalories per mol) (at 25 degrees) for sodium salts are: diethyl phosphate, minus 1.8 plus or minus 0.5; ethylene phosphate, minus 6.4 plus or minus 0.2; trimethylene phosphate, minus 3.0 plus or minus 0.2; tetramethylene phosphate, minus 2.2 plus or minus 0.1; methyl beta-D-ribofuranoside cyclic 3:5-phosphate, minus 11.1 plus or minus 0.2; methyl alpha-D-glucopyranoside cyclic 4:6-phosphate, minus 6.3 plus or minus 0.1; and cyclic adenosine 3:5-monophosphate (5-ester bond), minus 11.1 plus or minus 0.4 (10-minus 3 M Mg-2+). The enthalpy of hydrolysis of the 3-ester bond of cyclic adenosine 3:5-monophosphate (10-minus 3 M Mg-2+) has been revised to minus 11.1 plus or minus 0.2 kcal/mol from the value of minus 13.2 plus or minus 0.4 kcal/mol reported previously (greengard, p., rudolph, s.a., and sturtevant, j. m. (1969) j. biol. Chem. 244, 4798). All these values pertain to the hydrolysis of singly charged diesters to form singly charged monoesters. The data for the acyclic and monocyclic phosphodiesters are in qualitative agreement with their hydrolytic reactivities. The enthalpies measured for the hydrolysis of the glycoside cyclic phosphates cannot now be explained on the basis of their structures or reactivities; perhaps a contribution to the enthalpies by solvation or a previously unrecognized geometric strain effect may be responsible for the large exothermic enthalpies of these cyclic phosphate diesters. Changes in the heat capacity, increment Cp, for some of the hydrolytic reactions were also measured.

Cyclic AMP↗
PubMed1973

Diazoacetyl subtilisin.

Subtilisin reacts at pH 6.8-7.8 with p-nitrophenyl diazoacetate to release p-nitrophenol and form diazoacetyl subtilisin. Although at pH 7.8 this derivative rapidly undergoes hydrolytic cleavage to regenerate active enzyme, the derivative can be trapped by rapidly lowering the pH to 5. Similarly, with (14)C-labeled p-nitrophenyl diazoacetate, the corresponding radiochemically labeled diazoacetyl enzyme can be prepared. Photolysis of this radioactive derivative incorporates radioactivity into the protein, and subsquent hydrolysis gives rise to several radioactive components, which, however, have not yet been identified.

Acetates↗