PubMed Health⌕ Search

Biomedical subjects

A Radzicka

Publications and source records attributed to A Radzicka.

11 recordsLinked to original sources
PubMed1995

A proficient enzyme.

Orotic acid is decarboxylated with a half-time (t1/2) of 78 million years in neutral aqueous solution at room temperature, as indicated by reactions in quartz tubes at elevated temperatures. Spontaneous hydrolysis of phosphodiester bonds, such as those present in the backbone of DNA, proceeds even more slowly at high temperatures, but the heat of activation is less positive, so that dimethyl phosphate is hydrolyzed with a t1/2 of 130,000 years in neutral solution at room temperature. These values extend the known range of spontaneous rate constants for reactions that are also susceptible to catalysis by enzymes to more than 14 orders of magnitude. Values of the second-order rate constant kcat/Km for the corresponding enzyme reactions are confined to a range of only 600-fold, in contrast. Orotidine 5'-phosphate decarboxylase, an extremely proficient enzyme, enhances the rate of reaction by a factor of 10(17) and is estimated to bind the altered substrate in the transition state with a dissociation constant of less than 5 x 10(-24) M.

Catalysis↗
PubMed1994

On the probability of finding a water molecule in a nonpolar cavity.

Measurements of solubility and vapor pressure indicate that the cost of making a cavity in a nonpolar solvent that is large enough to accommodate a single water molecule is just balanced by the attraction between the water molecule and the walls of the cavity. As a result of this unexpected coincidence, the equilibrium constant for entry of an isolated water molecule from the vapor phase into cyclohexane is almost exactly unity at room temperature. Molecules smaller than water prefer the vapor phase, whereas molecules larger than water prefer cyclohexane. In equilibrium with liquid water, the tendency of single water molecules to enter small nonpolar cavities, such as may be present in mutant proteins, is expected to be vanishingly small.

Cyclohexanes↗
PubMed1993

Lack of water transport by amino acid side chains or peptides entering a nonpolar environment.

Water has been reported to enter cyclohexane in association with 3-methylindole, a model compound representing the side chain of tryptophan. Entrainment of water would cloud the interpretation of measured partition coefficients as a simple index of hydrophobicity. NMR and isotope-exchange experiments indicate that the reported entrainment of water resulted from unrecognized exchange of 3H from water into the -NH- group of the indole ring. A more detailed analysis shows that no significant amounts of excess water (less than 0.1 molecule/molecule of solute) enter cyclohexane with molecules representing the side chains of tryptophan, phenylalanine, threonine, lysine, or the peptide bond itself.

Amino Acids↗
PubMed1991

Analogues of intermediates in the action of pig kidney prolidase.

Dicarboxylic acids, resembling the collected substrates for the reverse peptide bond forming reaction, were bound several orders of magnitude more tightly than substrates, products, or previously known competitive inhibitors of reactions catalyzed by pig kidney prolidase (EC 3.4.13.9), a dipeptidase that cleaves peptide bonds to the nitrogen atom of proline. Other inhibitors containing a phosphoryl or phosphonyl group in addition to a carboxyl substituent were bound even more tightly, in a manner consistent with their possible resemblance to tetrahedral intermediates in substrate hydrolysis. These included several analogues of phosphoenol pyruvate, of which the most potent was (Z)-3-bromophosphoenolpyruvate (Ki = 4.6 x 10(-9) M). Ki values were found to vary with changing pH in a manner consistent with displacement of a hydroxide ion from the active site.

Animals↗
PubMed1988

Influences of solvent water on protein folding: free energies of solvation of cis and trans peptides are nearly identical.

Peptide bonds interact so strongly with water that even a modest difference between the free energies of solvation of their cis and trans isomers could have a significant bearing on protein structure. However, proton magnetic resonance studies at high dilution in deuteriated solvents show that N-methylformamide exists as the cis isomer to the extent of 8% in water, 10.3% in chloroform, 8.8% in benzene, and 9.2% in cyclohexane. Integrated intensities of proton and carbon resonances show that N-methylacetamide exists as the cis isomer to the extent of only 1.5% in water, not changing much in nonpolar solvents. Quantum mechanical calculations using the 6-31G basis set reproduce these relative abundances with reasonable accuracy and show that there is little difference between the dipole moments of the cis and trans isomers, for either amide. The remarkable insensitivity of cis/trans equilibria to the solvent environment and the heavy preponderance of trans isomers regardless of the polarity of the surroundings (ca. 98.5% for N-methylacetamide, whose properties may resemble those of a typical peptide bond) accord with the overwhelming preference of peptide bonds for the trans configuration that is consistently observed in the three-dimensional structures of globular proteins.

Acetamides↗
PubMed1987

New benzoquinone derivatives of dextran as carriers for interferon.

A series of derivatives of benzoquinone-2-sulfonic acid (I-VI) containing constituents of the structure of Cibacron Blue (CB) was synthesized and bound to dextran T 2000 with ether binding (VII-XII). Two dextran polymers XI and XII showed in biological assays high affinity for interferon (IFN).

Binding Sites↗
PubMed1982

Studies on the Ritter reaction. I. Synthesis of 3-/5-barbituryl/-propanesulfonic acids with anti-inflammatory activity.

Under the condition of the Ritter reaction the allyl group bound to C5 of the barbituric ring was observed to transform, due to addition of sulfuric acid, into beta-sulfooxy-propane-sulfonic or beta-hydroxy-propanesulfonic group. Inner anhydrides of the structure of beta-sulfone or carbyl sulfate are the intermediate products of these reactions. Well water-soluble calcium salts of the synthetized acids were pharmacologically analyzed.

Acetonitriles↗
PubMed1978

Synthesis of new sulfuric derivatives of allobarbital (5,5-diallylbarbituric acid) with anti-inflammatory activity.

It was found that allyl group of alkenes Ia-Ig is transformed into 3'-sulfo-2'-sulfatopropyl or beta-methyl-beta-sulton groups in reaction of addition under action of concentrated sulfuric acid in the presence of methyl cyanide. It was stated that this reaction is competitive to the Ritter reaction. Soluble in water calcium salts IV obtained from compounds Ia and Ib exhibited strong antiinflammatory activity.

Anti-Inflammatory Agents↗