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Biomedical subjects

I M Klotz

Publications and source records attributed to I M Klotz.

At least 19 recordsLinked to original sources
PubMed1996

Equilibrium constants and free energies in unfolding of proteins in urea solutions.

A novel thermodynamic approach to the reversible unfolding of proteins in aqueous urea solutions has been developed based on the premise that urea ligands are bound cooperatively to the macromolecule. When successive stoichiometric binding constants have values larger than expected from statistical effects, an equation for moles of bound urea can be derived that contains imaginary terms. For a very steep unfolding curve, one can then show that the fraction of protein unfolded, B, depends on the square of the urea concentration, U, and is given by [equation: see text] A12 is the binding constant as B-->0, and lambda is a parameter that reflects the augmentation in affinities of protein for urea as the moles bound increases to the saturation number, n. This equation provides an analytic expression that reproduces the unfolding curve with good precision, suggests a simple linear graphical procedure for evaluating A12 and lambda, and leads to the appropriate standard free energy changes. The calculated delta G degree values reflect the coupling of urea binding with unfolding of the protein. Some possible implications of this analysis to protein folding in vivo are described.

Protein Folding↗
PubMed1993

A perspective into ligand-receptor affinities using complex numbers.

The binding of ligands by a receptor can be expressed in an equation derived by a thermodynamic stoichiometric approach in which the stoichiometric equilibrium constants are all positive and real. An alternative binding equation can be derived algebraically in which the equilibrium constants can have values that are complex numbers. Some consequences of this situation are explored, and numerical values of the ghost equilibrium constants are evaluated for a number of ligand-receptor complexes.

Animals↗
PubMed1993

Biogenesis: number mysticism in protein thinking.

Historically, great minds have been tantalized by the idea that integers contain hidden, subtle meanings that could give us deep insights into natural (and supernatural) phenomena. Numerological analysis has been used in religion, mythology, and the sciences. In the field of proteins, integers played a stimulating role during early struggles to unravel structure, but they ultimately proved constrictive and misleading. In contrast, the introduction of imaginary (or complex) numbers into the algebra and numerical analysis of ligand-protein affinities can open new perspectives into such interactions.

Amino Acid Sequence↗
PubMed1987

O-carbamoylsalicylates: agents for modification of hemoglobins.

To combine the attractive features of cyanate and of O-acetylsalicylate as hemoglobin-modifying agents we have prepared carbamoylsalicylate. This compound is a close analogue of aspirin and also resembles a masked cyanate. O-Carbamoylsalicylate and some related carbamates modify hemoglobin substantially, even at 5 mM concentration.

Antisickling Agents↗
PubMed1985

Specific chemical modifications in the beta-cleft site of hemoglobin. Potential anti-sickling agents with hybrid functionalities.

Ester and aldehyde groups have been combined to produce molecules with hybrid functionalities that might be effective in modifying hemoglobin. In this series of compounds, the reagents that carry the combination of an anionic charge and an aldehyde as binding groups show a strong preference for the beta-cleft region of the protein and produce selective modification therein. 5-Formylaspirin and related oxalyl, malonyl, and fumaryl monoaldehyde monoester derivatives form a new class of substances for which modification of hemoglobin is very substantial and is inhibited by inositol hexaphosphate.

Acylation↗
PubMed1985

Pharmacological actions of diaspirins, potential antisickling agents: analgesic and anti-inflammatory effects.

Three aspirin analogs, dibromoaspirin, bis(3,5-dibromosalicyl) succinate and bis(3,5-dibromosalicyl) fumarate, potential antisickling agents, were compared with acetylsalicylic acid (aspirin) for their analgesic, body temperature and anti-inflammatory effects in the laboratory mouse and rat. In the analgesic assay, using the "writhing method", only a 200 mg/kg dose of the diaspirin succinate significantly reduced the writhing response induced by phenylacetic acid. Only a dose of 800 mg/kg of acetylsalicylic acid significantly decreased writhing. These analog compounds had only slight hypothermic effects, the reduction in body temperature not being appreciable. On the other hand, they were effective anti-inflammatory agents, comparable to aspirin; a dose of 200 mg/kg very significantly reduced the paw edema due to injected carrageenan.

Analgesics↗
PubMed1984

Mathematical models for ligand-receptor binding. Real sites, ghost sites.

In the basic life sciences the term "model" implies a physical, chemical, or molecular construct that provides a representation for the interpretation of experimental observations. To the statistician, however, a model is a mathematical expression for correlating data, which may or may not have roots in a molecular picture. With regard to ligand-receptor interactions, the mathematical model used plays a crucial role in extrapolations of binding measurements. Regardless of the statistical goodness of fit of data to an equation, the relationships of the parameters of a mathematical formalism to the molecular features of ligand-receptor complexes are generally very complex. Oversimplified interpretations of the molecular significance of the constants derived from binding measurements are unwarranted, unless one has independent information from molecular probes.

Kinetics↗
PubMed1984

Alternative diaspirins for modification of hemoglobin and sickle hemoglobin.

Studies of modification of hemoglobin and of sickle hemoglobin by alternative aspirins have been extended to a series of new bis esters with a variety of substituted bridging diacids and to a group of mono esters with polar acyl groups. Rates of hydrolysis of these alternative aspirins have also been examined, and they reveal that a careful balance between stability and reactivity is essential for optimal activity. Four-carbon bridging groups have been found to be particularly effective, two of these raising the minimum gelling concentration of sickle hemoglobin by as much as 100%.

Adult↗
PubMed1984

Diaspirins of methylenecitric acid.

A series of bissalicylic esters of methylenecitric acid have been prepared and, as a probe of their potential as antisickling agents, tested for their ability to modify hemoglobin. Substantial acylation of hemoglobin was obtained with these dicarboxylate esters at 1-5 mM concentrations.

Antisickling Agents↗
PubMed1984

Electrostatic effects in acylation of hemoglobin by aspirins.

Carboxylate substituents added to the salicylate ring increase the effectiveness of a variety of aspirins and diaspirins in acylating hemoglobin. Even more effective are a series of monoesters of dicarboxylate derivatives. Bis(5-carbomethoxysalicyl)fumarate and -succinate at 5 mM concentrations modify approximately 100% of the hemoglobin in solution and should alter the aggregation behavior of sickle hemoglobin.

Acylation↗