Phosphate ligands

Ca2+ Carboxylate, particularly gla proteins less affinity than Mg2+ for nitrogen ligands phosphate... 

Ligands also differ in their ability to form stable complexes. The ligands phosphate, hydroxide, carbonate, and so forth, are potent complex formers while the perchlorate, CIO4", and nitrate, NO3", ions show very little tendency to form complexes. It is for this reason that nitrate or perchlorate salts are used as swamping electrolytes in experiments where it is desirable to have a constant ionic strength. ... 

Fig. 10. Pharmacophores for angiotension-converting enzyme. Distances in nm. (a) The stmcture of a semirigid inhibitor and distances between essential atoms from which one pharmacophore was derived (79). (b) In another pharmacophore, atom 1 is a potential zinc ligand (sulfhydryl or carboxylate oxygen), atom 2 is a neutral hydrogen bond acceptor, atom 3 is an anion (deprotonated sulfur or charged oxygen), atom 4 indicates the direction of a hydrogen bond to atom two, and atom 5 is the central atom of a carboxylate, sulfate, or phosphate of which atom 3 is an oxygen, or atom 5 is an unsaturated carbon when atom 3 is a deprotonated sulfur. The angle 1- -2- -3- -4 is —135 to —180° or 135 to 180°, and 1- -2- -3- -5 is —90 to 90°.

In both structures the ion is coordinated to six ligands with octahedral geometry. Four water molecules as well as the side chain oxygen atom of a serine residue from the P-loop and one oxygen atom from the (3-phosphate bind to Mg + in the GDP structure. Two of the water molecules are replaced in the GTP structure by a threonine residue from switch I and an oxygen atom from the y phosphate (similar to the arrangement shown in... 

A recently discovered reduction procedure provides a convenient route to axial alcohols in cyclohexyl derivatives (5). The detailed mechanism of the reaction remains to be elucidated, but undoubtedly the reducing agent is an iridium species containing one or more phosphate groups as ligands. In any case, it is clear that the steric demands of the reducing agent must be extraordinary since the stereochemical outcome of the reaction is so specific. The procedure below is for the preparation of a pure axial alcohol from the ketone. 

Other types of complexons for polyanions (e.g. polycarboxylates and phosphates) are linear ligands with polyguanidinium cations or polyammonium cations as functional groups 33). 

The introduction of another organic cation function, guanidinium group, into macrocyclic structures such as (IV)-(VI) produces ligands which also display affinity for phosphate anions58). 

The platinum(IV) compound that has shown most promise is carboplatin (paraplatin), which received FDA approval in 1990. Features to note in its structure are the use of hydroxy and carboxylate groups to improve water solubility. As noted above, the ammine ligand has been found to need at least one hydrogen, possibly for hydrogen-bonding to phosphate groups in the DNA (Figure 3.116). 

An early observation that 2 -d-3 -AMP was a more potent inhibitor of adenylyl cyclases than 2 -d-Ado suggested that the enzyme would accept substitutions at the 3 -ribose position and that phosphate was particularly well tolerated. This led to the generation of a family of 3 -phosphoryl derivatives of 2, 5 -dideoxyadenosine exhibiting ever greater inhibition with the addition of an increasing number of 3 -phosphoryl groups, the most potent of which is 2, 5 -dideoxyadenosine-3 -tetraphosphate (2, 5 -dd-3 -A4P Table 4) [5]. These constitute a class of inhibitors historically referred to as P -site ligands that caused inhibition of adenylyl... 

Probably all adenylyl cyclases are inhibited competitively by substrate analogs, which bind at the site and to the enzyme configuration with which cation-ATP binds (cf Fig. 4). One of the best competitive inhibitors is (3-L-2, 3 -dideoxy adenosine-5 -triphosphate ( 3-L-2, 3 -dd-5 -ATP Table 4) [4], which allowed the identification of the two metal sites within the catalytic active site (cf Fig. 4) [3]. This ligand has also been labeled with 32P in the (3-phosphate and is a useful ligand for reversible, binding displacement assays of adenylyl cyclases [4]. The two inhibitors, 2, 5 -dd-3 -ATP and 3-L-2, 3 -dd-5 -ATP, are comparably potent... 

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