Reversible chemical modifications

There are essentially two types of control mechanisms for biochemical switching allosteric cooperative transition and reversible chemical modification. Allosteric cooperativity, which was discussed in Chapter 4, was discovered in 1965 by Jacques Monod, Jefferies Wyman, and Jean-Picrrc Changeux [143], and independently by Daniel Koshland, George Nemethy and David Filmer [116]. The molecular basis of this phenomenon, which is well understood in terms of three-dimensional protein crystal structures and protein-ligand interaction, is covered in every biochemistry textbook [147] as well as special treatises [215],... 

Reversible chemical modification of enzymes, which was discovered in 1955 by Edmond Fischer and Edwin Krebs [58], is a more prevalent mechanism for cellular signaling switching. Fischer and Krebs showed that enzymes can be turned from an inactive form to an active form via phosphorylation of certain residues of the protein. Enzymes that catalyze phosphorylation (addition of a phosphate group coupled with ATP or GTP hydrolysis) are called protein kinases. Enzymes that catalyze dephosphorylation (which is not the reverse reaction of the phosphorylation) are called phosphatases. For example, a protein tyrosine phosphatase is an enzyme that catalyzes the removal of a phosphate group from a tyrosine residue in a phosphorylated protein [57],... 

Quandt L and Huth W (1984) Modulation of rat-liver mitochondrial acetyl-CoA acetyl-transferase activity by a reversible chemical modification with coenzyme A. Biochim-ica et BiophysicaActa 784,168-76. 

Holmgren, A. Reversible Chemical Modification of the Tryptophan Residues of Thioredoxin from Escherichia coli B. Eur. J. Biochem. 26, 528-534 (1972). 

Previero, A., M. A. Coletti-Previero, and J. C. Cavadore A Reversible Chemical Modification of the Tryptophan Residue. Biochim. Biophys. Acta 147, 453-461 (1967). 

Further chemical modification of the phenylpiperidine moiety has proven unusually fruitful in producing medicinal agents that affect the central nervous system. First, a series of compounds loosely related to the reversed meperidines produced several drugs with important antipsychotic activity. Further discussion of this pharmacologic activity, often referred to as major tranquilizer activity, will be found in the section on phenothiazines. The group led by Janssen took advantage of the chemistry of the... 

Most ester-forming reactions are reversible. Depending on circumstances, these reactions may be either undesirable side reactions, for example hydrolytic chain scissions occurring during processing, or useful reactions when chemical modification or polymer recycling is considered. 

Reversed-phase PLC precoated plates are based on silica gel matrices with chemical modifications in such a manner that the accessible polar, hydrophilic silanol groups at the silica gel surface are replaced by nonpolar, hydrophobic alkyl chains via silicon-carbon bonds. For preparative purposes, up to now only PLC precoated RP plates with C-18 modification are available. This abbreviation is often also designated as RP-18, meaning that an octadecyl alkyl chain is chemically bonded to the silica gel surface. 

In a sense each monolithic column is unique, or produced as a product of a separate batch, because the columns are prepared one by one by a process including monolith formation, column fabrication, and chemical modification. Reproducibility of Chro-molith columns has been examined, and found to be similar to particle-packed-silica-based columns of different batches (Kele and Guiochon, 2002). Surface coverage of a Chromolith reversed-phase (RP) column appears to be nearly maximum, but greater silanol effects were found for basic compounds and ionized amines in buffered and nonbuffered mobile phases than advanced particle-packed columns prepared from high purity silica (McCalley, 2002). Small differences were observed between monolithic silica columns derived from TMOS and those from silane mixtures for planarity in solute structure as well as polar interactions (Kobayashi et al., 2004). 

Antibodies. The reaction between an antibody and its antigen does not result in the chemical modification of the antigen compared with the action of an enzyme and provides the basis for producing chromatographic media capable of selecting the complementary molecules. Either the antigen is insolubilized and used to isolate and purify the appropriate antibodies or with the increased availability of monoclonal antibodies, the reverse procedure is used. 

To answer this question, information obtained from studies of irreversible systems needs to be examined. Irreversible protein processes may occur as a result of intermolecular interactions (i.e., aggregation, chemical modification, intermolecular cross-linking). Although an attempt is generally made to search for conditions that provide maximal reversibility, perhaps by altering the solution conditions (i.e., pH, salt content, lowering the protein concentration) that minimize contact and electrostatic interactions, many systems can still exhibit little or no reversibility. This would be the case for the core protein obtained by limited... 

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