Acetate binding

Thomas CP, Liu KZ, Vats HS. Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate (alpha ENaC and sgkl expression in renal collecting duct epithelia. Am J Physiol Renal Physiol 2005 . 

Figure 21. 2-Guanidiniocarbonylpyrrole with proposed solution and solid-state acetate binding modes.

Schmuck, C., Lex, J. (1999) Acetate binding within a supramolecular network formed by a guanidiniocarbonyl pyrrole cation in the solid state, Org. Lett. 3, 1253-1256. 

A list of drugs that bind more or less equally to the p-nitrophenyl-acetate binding site and one noninhibitory site, with dissociation constants differing by no more than a factor of two is given in Table III. At present very little is known about these other sites, e.g. even the total number of such sites is not known. 

As mentioned earlier, the binding sites of HSA have not been characterized well and it is not clear what these compounds have in common that would cause each of them to interact with the nitrophenyl acetate binding site (see Scheme II). Furthermore it is not clear whether the other site with which each of them interacts is the same site or a series of four different sites. To help shed light on this latter question we have determined the effect of each on the inhibition of the others. 

Acetate binding produces the same type of spectral changes as other anions, demonstrating that exogenous ligand binding occurs by substitution for the solvent. 

In the presence of human serum albumin, the H spectrum of acetyl-salicyclic acid is specifically shifted and broadened [119]. The interpretation of changes in T, and T2 require several theoretical assumptions. These have been discussed in detail [120] for JV-acetylsulphanilamide and acetate binding to the active site of carbonic anhydrase. It was concluded that the acetyl groups of these inhibitors have a motion additional to that of the enzyme. It can be shown by NMR that acetate binds to two sites on the enzyme, only one of which is inhibitory to esterase activity (methyls are 4.3 and 4.8 A from the metal in the Mn substituted enzyme [121]). Strict care must be taken to avoid paramagnetic impurities when NMR relaxation enhancement by diamagnetic macromolecules is being studied. A preparation of carbonic anhydrase, for example, can contain 0.24 paramagnetic Cu atoms per Zn atom [122]. 

This question can be answered affirmatively by citing recent work of Breslow et al. (13), who were interested in the acylation of (5-cyclodextrins (CD) by bound esters. When, for example, m-nitrophenyl acetate binds to the -CD cavity, the ester transfers its acyl group 64 times faster than it hydrolyzes in water at the same pH ... 

Coordination is expected in both cases, and so loss of CU is necessary to produce an xf form the conductivity should be high for the ionic species, and the IR of the two acetate binding modes are also different. Comparison of the IR with literature examples would be needed to distinguish the two cases. 

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