Multivalent inhibition

Although significant levels of multivalent inhibition have been measured for two different enzymes in the presence of dodecavalent glycosylated C60 fullerenes, more investigations have to be performed to rationalize these promising results and optimize the combination of multivalency and glycomimetic for novel antibacterial agents. 

The retention of potent enzyme inhibition and in vitro antiviral activity in the presence of functionalisation with relatively long hydrophobic chains at C-7 of zanamivir has been exploited in the development of di- and poly-valent structmes carrying zanamivir (reviewed in Sun 2007). Multivalent presentation of drug may... 

Bai J, Rossi J, Akkina R (2001) Multivalent anti-CCR ribozymes for stem cell-based HIV type 1 gene therapy. AIDS Res Hum Retroviruses 17 385-399 Bai J, Sui J, Zhu RY, TaUarico AS, Gennari F, Zhang D, Marasco WA (2003) Inhibition of Tat-mediated transactivation and HIV-1 replication by human anti-hCychnTl intrabodies. J Biol Chem 278 1433-1442... 

Xanthine oxidase (XO) is not only an important biological source of ROS but also the enzyme responsible for the formation of uric acid associated with gout leading to painful inflammation in the joints. The XO inhibition effect by the enzymatically synthesized poly(catechin) increased as an increasing concentration of catechin units, while the monomeric catechin showed almost negligible inhibition effect in the same concentration range. ° This markedly amplified XO inhibition activity of poly(catechin) was considered to be due to effective multivalent interaction between XO and the condensed catechin units in the poly (catechin). 

The PL-catechin conjugate showed greatly amplified concentration-dependent inhibition activity against bacterial collagenase (ChC) on the basis of the catechin unit, which is considered to be due to effective multivalent interaction between ChC and the catechin unit in the conjugate. The kinetic study suggests that this conjugate is a mixed-type inhibitor for ChC. Hyaluronidase is an enzyme which catalyzes hydrolysis of hyaluronic acid and is often involved in a number... 

D. Page, D. Zanini, and R. Roy, Macromolecular recognition Effect of multivalency in the inhibition of binding of yeast mannan to concanavalin A and pea lectins by mannosylated dendrimers, Bioorg. Med. Chem., 4 (1996) 1949-1961. 

The deprotected lactosides were evaluated as inhibitors against lectin binding in a solid-phase inhibition assay with immobilized ASF on the surface of microtiter plate wells, mimicking cell-surface presentation, while mammalian galectins-1, -3, and -5 were in solution. Strong multivalency effects and selectivity were observed for the... 

T. K. Lindhorst, C. Kieburg, and U. Krallmann-Wenzel, Inhibition of the type 1 fimbriae-mediated adhesion of Escherichia coli to erythrocytes by multiantenn-ary x-mannosyl clusters the effect of multivalency, Glycoconjug. /., 15 (1998) 605-613. 

Concerted Feedback Inhibition Concerted feedback inhibition, also called multivalent feedback inhibition, is the limiting case of synergistic feedback inhibition. In this case neither end product alone will inhibit the target enzyme. However, when both are present, inhibition is observed. 

Additional information <1, 7-9, 12-17, 21> (<7> inhibitory effect of phosphonate analogues of 1,3-diphosphoglycerate, overview [49] <21> no effect by glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-phosphate, pyruvate, phosphoenolpyruvate and lactate [70] <13> double-inhibition studies, kinetics, modeling of inhibitor binding, e.g. phosphate [55] <13> enzyme is regulated by multivalent anions, overview [55] <8> no inhibition by Hg [25] <1,7,9,12-17> yeast enzyme is insensitive to thiol reagents [17]) [17, 25, 49, 55, 70]... 

Paulus, H. Gray, E. Multivalent feedback inhibition of aspartokinase in Bacillus polymyxa. I. Kinetic studies. J. Biol. Chem., 242, 4980-4986 (1967)... 

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