Affinity enhancing modulators

Frenander U, Jonsson AS (1996) Cell harvesting by cross-flow microfiltradon using a shear-enhanced module. Biotechnol Bioeng 52(3) 397-403 Galaev lY (1999) New methods of protein purification. Affinity ultrafiltradon. Biochemistry... 

N-Myristoylation is achieved by the covalent attachment of the 14-carbon saturated myristic acid (C14 0) to the N-terminal glycine residue of various proteins with formation of an irreversible amide bond (Table l). 10 This process is cotranslational and is catalyzed by a monomeric enzyme called jV-myri s toy 11ransferase. 24 Several proteins of diverse families, including tyrosine kinases of the Src family, the alanine-rich C kinase substrate (MARKS), the HIV Nef phosphoprotein, and the a-subunit of heterotrimeric G protein, carry a myr-istoylated N-terminal glycine residue which in some cases is in close proximity to a site that can be S-acylated with a fatty acid. Functional studies of these proteins have shown an important structural role for the myristoyl chain not only in terms of enhanced membrane affinity of the proteins, but also of stabilization of their three-dimensional structure in the cytosolic form. Once exposed, the myristoyl chain promotes membrane association of the protein. 5 The myristoyl moiety however, is not sufficiently hydrophobic to anchor the protein to the membrane permanently, 25,26 and in vivo this interaction is further modulated by a variety of switches that operate through covalent or noncovalent modifications of the protein. 4,5,27 In MARKS, for example, multiple phosphorylation of a positively charged domain moves the protein back to the cytosolic compartment due to the mutated electrostatic properties of the protein, a so-called myristoyl-electrostatic switch. 28 ... 

An understanding of Fey receptor gene polymorphism explains why some patients do not respond to monoclonal antibody, and it may broaden our understanding of monoclonal antibody activity and improve treatment outcomes in the future. Specific strategies include modulation of Fey receptor affinity or introduction of Fey receptor-reengineered monoclonal antibody designed to enhance binding to the Fey receptor. 

The TET-induced inhibitory influence on cyclic 3 ,5 -AMP phosphodiesterase (PDE) activities precedes edema formation in the rat brain [74]. lb clarify the mechanism of the protective action of EGb against TET-toxidty in rats, in vitro and ex vivo effects of EGb on PDE activities of cerebral tissue were investigated [75]. Higher concentrations of EGb (5-250 mg/L) inhibited the PDE activity in the brain in normal rats, whereas lower concentrations (0.25-4.0 mg/L) of EGb enhanced the activity of the enzyme. The inhbitory effect of TET on the high affinity PDE activity (measured with 0.25 ftM cyclic AMP) of the brain was diminished in the presence of low EGb concentrations. Furthermore, preventive and curative treatment of 1 El-poisoned rats with EGb (100 mg/kg, p.o., for 7 days) prevented both the formation of edema and the fall of PDE activity induced by TET alone. These results suggested the antiedema action of EGb might be partly associated with its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE. 

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