Haloacetol phosphates

Most of the methodologies used and problems encountered with halo-ketones as affinity labels are covered by considerations of bromopyruvate, haloacetol phosphates, and haloketone derivatives of pyridine nucleotides. Similar information is gained from numerous elegant studies in which halomethylketone derivatives of amino acids and peptides have been used as affinity labels for proteases. These investigations are excluded from the present article, since they are considered elsewhere in this volume. ... 

These compounds are close structural analogs of dihydroxyacetone phosphate, differing only in replacement of the hydroxyl with a halogen. The rationale for designing haloacetol phosphates was much the same as that which led Meloche to believe that bromopyruvate would be a likely affinity label for kdGtP aldolase. Reactions catalyzed by both... 

The most successful application of haloacetol phosphates as affinity labels has been in the partial characterization of the active site of triosephosphate isomerase. Very similar studies, carried out independently in the laboratories of F. C. Hartman and J. R. Knowles, demonstrated an essential glutamyl y-carboxylate (esterified by the reagent) in the enzyme. The recently determined primary structure of the enzyme from rabbit muscle places the glutamyl at position 165. All the usual criteria of affinity labeling were satisfied and have been well documented. Certain aspects of these studies that either relate to the use of haloketones in general or have provided evidence of the carboxylate s intimate role in the catalytic process will be considered. 

Haloacetol phosphates, 139-145 Haloacetyl derivatives, 153-157, 627 labeling with, 554-561 u Halogenalkylacetates, 251 a-Haloketones, 130-153 as reagents, disadvantages, 131 Halomethyl ketones, 197-208 as alkylating agents, 197, 204 derivatives of amino acids and peptides, 201... 

Another class of potential inhibitors is the haloacetol phosphates of bromine, chlorine, and iodine. Hartman showed that there was irreversible binding of these compounds to the substrate active site of triose-phos-phate isomerase because of structural similarities to dihydroxyacetone phosphate.Subsequent work with isolated wheat chloroplasts has indicated that iodoacetol phosphates enter the chloroplast by the phosphate translocator and primarily inhibit glyceraldehyde-3-phosphate dihydro-... 

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