Phosphate mimicks

The complex with ADP and aluminium fluoride is thought to resemble the early ADP.Pi state immediately after hydrolysis, whereas the complex with ADP and vanadate may represent a late state in which the phosphate (mimicked by vanadate) has moved quite a long distance (15 A) from the active center to the surface of the motor domain. There it is fixed by two hydrogen bonds to the solvent exposed tips of the switch-1 loop region (L9) at one side and the switch-2 loop (Lll) at the other side. 

In 1970, Eckstein and co-workers reported the first stereochemical study of an enzyme-catalyzed hydrolysis of a phosphate ester, the hydrolysis of the endo isomer of uridine 2, 3 -cyclic phosphorothioate (enrfo-cyclic UMPS) (72) by ribonuclease A (RNase A) 13). The hydrolysis of RNA catalyzed either by base or by RNase A proceeds by a two-step mechanism in which the 2 -hydroxyl group of a nucleotide unit within an RNA molecule acts as a nucleophile on the 3 -phosphodiester bond to displace the 5 -hydroxyl group of the neighboring nucleoside to form a 2, 3 -cyciic phosphate intermediate. RNase A then catalyzes the hydrolysis of this cyclic phosphate, mimicked by Eckstein s endo-cyclic UMPS, to yield the ultimate 3 -mononucleotide product. 

Scheme 6.14 Pol) phosphates mimicking nucleic and teichoic acids.

Mossbauer spectroscopic titration of [Me2Sn(IV)] and [MesSnflV)] hydroxides with ligands mimicking nucleic acid phosphate sites and with native DNA was the aim of work by Barbieri et al. A series of aqueous solutions of each system, formed by the organotin(IV) hydroxides and the phosphate ligands used... 

Semiempirical calculations on the interaction between [Me2Sn(IV)] and a dinuclide triphosphate duplex (DD), mimicking a DNA model system, were performed with the PM3 method and published by Barbieri et al. The results indicate that the [Me2Sn(IV)] moiety binds to two adjacent phosphate groups. 

In spite of the above mentioned Co(EII) compounds, kinetically labile metal complexes may provide fast product/substrate exchange and some of these systems show real catalytic activity. In native dinuclear phosphatases Mg(II), Mn(II), Fe(II/III), or Zn(II) ions are present in the active centers. Although the aqua complexes of the weakest Lewis acids, Mg(H) and Mn(II), show measurable acceleration of e.g. the transesterification of 2-hydroxypropyl p-nitrophenyl phosphate HPNP, [Mn(II)] = 0.004 M, kobs/ uncat = 73 at pH 7 and 310 K, [38] or the hydrolysis of S -uridyluridine (UpU) [39], only a few structural [40] but no functional phosphatase-mimicking dinuclear complexes have been reported with these metal ions. 

Transition states of this tetrahedral nature have now been mimicked effectively by a range of stable analogues, including phosphonic acids, phosphonate esters, a-difluoroketones, and hydroxymethylene functional groups (Jacobs, 1991). Lerner s group elicited antibodies to a tetrahedral anionic phosphonate hapten [3] (Appendix entry 2.9)2 whilst Schultz s group isolated a protein with high affinity for p-nitrophenyl cholyl phosphate [4] (Fig. 4) (Appendix entry 3.2). 

The two-step mechanism of phosphate ester hydrolysis by the (Znn)2-containing alkaline phosphatase (AP) (7) is thus somewhat mimicked by 24. The phosphoryl intermediate 25 is generated by nucleophilic attack of the alkoxide moiety in 24b at BNP" and is hydrolyzed by the intramolecular Zn11—OH" species in 25b. Thus, the attack at the BNP... 

Several approaches to artificial photosynthesis involve the mimicking of membranes to effect charge separation. An easy extension of the micellar effects described above to systems amenable to study as photosynthetic models can be encountered in the charge separation derived on synthetic vesicles or membranes (275). Sonic dispersal of long chain ammonium halides, phosphates, sulfonate, or carboxylates produces prolate ellipsoidal vesicles with long term stabilities which can entrain and trap molecules in their compartments. With donor-acceptor photosystems, four physical arrangements about the vesicle are important, Fig. 6. 

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