2-3-Diphosphoglycerate

Six coordinate iron(III) may be bound by either one molecule of a hexadentate drug, two molecules of a tridentate drug, three molecules of a bidentate drug, six molecules of a monodentate 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

From stability constant measurements, log K = 2.3 mol ) . (32,33) The equilibrium therefore favors the hexadentate chelate for all but extreme ligand concentrations. 

The second component of the chelate effect, the concentration factor, can be Illustrated by considering the ability of a drug (D) to sequester transferrin-bound iron  

The same property is illustrated by the data in Table II which compares the degrees of dissociation of tetracoordlnate complexes with 0, 2, and 3 chelate rings. A chelate effect of 10 per chelate ring is assumed as the basis for the arbitrary stability constants listed. The superior properties of the metal chelate in dilute solution are dramatically Illustrated by a simple calculation of the degrees of dlssoclaton in 1.0 molar and 

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Other 2,3-Diphosphoglycerate Pocket Cross-Linkers. The reactivity of the valine NAl(l)a and lysine EF6(82)p residues in the 2,3-DPG pocket shown by NFPLP and (bis-PL)P4 has stimulated the search for other reagents that react similarly but have potential for greater efficiency and ease of scaleup. The systematic study of four different dicarboxyhc acid derivatives, cross-linked in both oxygenated and deoxygenated conditions, has been reported (92). Each of these derivatives presents problems in purification, and proof of the sites of reaction is tedious. 

The 3D structure of the 2,3-diphosphoglycerate (DPG) complex of hemoglobin (Hb) served to derive simple aromatic dialdehydes that mimic the function of DPG as an allosteric modulator of the oxygen affinity of Hb. Some of the resulting compounds were as active and even more active than DPG, the natural ligand [1-3]. 

Based on Arnone A X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhemoglobin. Nature 1972 237 146. Reproduced with permission.)... 

Diphosphoglycerate A compound in red blood cells that affects oxygen binding to and release from hemoglobin. 

M26. Miwa, S., Luzzatto, L., Rosa, R., Paglia, D. E., Schroter, W De Flora, A., Fujii, H., Board, P. G and Beutler, E., International Committee for Standardization in Haematology Recommended methods for an additional red cell enzyme (pyrimidine 5 -nucleotidase) assay and the determination of red cell adenosine 5 -triphosphate, 2,3-diphosphoglycerate and reduced glutathione. Clin. Lab. Haematol. 11, 131-138 (1989). 

Goodford PI, St-Louis J, Wootton R. A quantitative analysis of the effects of 2,3-diphosphoglycerate, adenosine triphosphate and inositol hexaphosphate on the oxygen dissociation curve of human haemoglobin. J Physiol 1978 283 397. 

Although P MRS can be used to measure pH in isolated, perfused hearts, it is not suitable in vivo because 2,3-diphosphoglycerate in ventricular blood interferes with the myocardial Pi resonance. Schroeder et al. have developed a possible alternative method for in vivo use based on the carbonic-anhydrase-catalyzed, pH-dependent equilibrium of CO2 and HCO3. Infusion of h)q)erpolarized 1- C-pyruvate generates strong signals of metabolically produced C02 and H COJ to yield pH by the Henderson-Hasselbalch equation. Applicability of the method in humans remains to be demonstrated. 

P NMR is a most valuable technique. Not only can it be used to titrate the pKa values of phosphates, but it can also be used to measure the ionization of known phosphate residues in vivo, such as those of 2,3-diphosphoglycerate, and thus to determine intracellular pH.21... 

Figure 10.11 Binding of 2,3-diphosphoglycerate (DPG) between the f3 chains in the central cavity of human hemoglobin. [From A. Amone and M. F. Perutz, Nature, Land. 249, 34 (1974).]...

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