Catechol binding site

Ligand 3.147 is part of the class of siderands (synthetic siderophores), and displays further useful properties such as stability towards oxidation of the catechol binding sites and hydrolysis resistance. This represents one of the few examples where man-made molecules are more effective than their natural precursors. 

According to this theory put forward in 1974, the relative order of activity of the isomers viz., R(-) isomer epinephrine, S(+) isomer epinephrine and epinine deoxy isomer on the adrenergic receptors are in the order of R > S deoxy. Besides, the R isomer can bind to all the three sites, namely (i) catechol binding site A ( ) hydroxy binding site B and Hi) anionic binding site C as illustrated below whereas the S isomer and the deoxy isomer, that essentially exhibit practically identical biological activity, can exclusively bind to two of the sites. 

In fact, the majority of the radiolabel was recovered in the small C-terminal fragment containing TM-6 and TM-7. It delivered biochemical evidence that the aryloxyalkyl side-chain of salmeterol was positioned in that region and represented a secondary binding site, while the pharmacophore portion of the compound bound to the expected catechol site. 

Fig. 2.12 Examples of non-linear Arrhenius (or Eyring) plots (a) 1u(A oh)7 " ) vs T for the base hydrolysis of trans-Co(en)2ClJ. Curvature may result when k, k2 and A// , not equalling A// in the conjugate-base mechanism (Sec. 4.3.4). Reprinted with permission from C. Blakeley and M. L. Tobe, J. Chem. Soc. Dalton Trans. 1775 (1987). (b) nk vs T for iron removal from C- and N-terminal monoferric transferrin (lower and upper scales respectively). Transferrin contains two iron binding sites = 35 A apart. Either of the two sites, designated C- and N-terminal, can be exclusively labelled by Fe(lll) ions and these may be removed by a strong ligand such as a catechol (see Sec. 4.11). Reprinted with permission from S. A. Kretschmar and K. N. Raymond, J. Amer. Chem. Soc. 108, 6212 (1986). (1986) American Chemical Society.

Tris(bpy) complexes of ruthenium(II) with pendant catechol units are represented by [Ru(bpy)2(114)], isolated as the BF4 salt. Interest in this fluorescent complex stems from its use as a potential skin sensitizer. " In the complex [Ru(bpy)2(115)] + (R = H), the deprotonated catechol unit can act as a binding site for other metal fragments, thereby forming homo- and... 

Other Proteins The ouabain-binding site on (Na /K -adenosine-5 -triphosphatase, 46, 523 penicillin isocyanates for /3-lactamase, 46, 531 active site-directed addition of a small group to an enzyme the ethylation of ludferin, 46, 537 mandelate racemase, 46, 541 d imethylpyrazole carboxamidine and related derivatives, 46, 548 labeling of catechol O-methyltransferase with N-haloace-tyl derivatives, 46, 554 affinity labeling of binding sites in proteins by sensitized photooxidation, 46, 561 bromocolchicine as a iabei for tubuiin, 46, 567. 

Swaminath, G., Deupi, X., Lee, T. W., Zhu, W., Thian, F. S., Kobilka, T. S., and Kobilka, B. K. (2005). Probing the / 2-adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists. / Biol. Chem. 280, 22165-22171. 

Two binding sites are commonly found catecholate, as in enterobactin, and hydroxamate, the motif in desferrioxamine B. The resulting complex is targeted by a membrane-bound receptor and captured by the organism. The complex is transported across the cell membrane where the iron is reduced to iron(II), which has a lower affinity for the siderophore, and subsequently decomplexed. 

The effective molarity measured for [Phen2]PAAcPEI may be compared with that for enterobactin, the strongest microbial siderophore, containing three catechol units connected by a spacer. The effective molarity of a catechol unit towards a Fe(m) ion bound to another catechol unit contained in enterobactin is estimated to be 3 x 104 m [37]. Enterobactin contains three catechol units, whereas the Cu(ii) binding site of [Phen2]-paAcPEI consists of only two phenanthrolines. Nevertheless, the effective molarity observed for [Phen2]PAAcPEI is extraordinary for a synthetic system. 

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