- Synthesis of new photoaffine probes on the basis of ganglioside GM1
-
New photoaffine probes, photoreactive derivatives of ganglioside GM1 bearing a carbene-generating diazocyclopentadien-2-ylcarbonyl group at various distances from the carbohydrate moiety in their molecules were synthesized.
- Tsibizova,Vodovozova,Mikhalyov,Molotkovsky
-
-
Read Online
- One-step iodination of the diazocyclopentadien-2-ylcarbonyl group - A new and convenient preparation of effective radiolabelled photoaffinity probes
-
A detailed study devoted to direct iodination of the photoactivatable diazocyclopentadien-2-ylcarbonyl (Dcp) group is presented. The iodination does not influence the high carbene reactivity of the Dcp-generated carbene. It was shown that the Dcp substituent forms 4-mono-, 5-mono- and 4,5-diiododerivatives upon iodination under oxidative conditions (76, 20 and 4%, respectively, when DcpOMe 2 is iodinated). Photolysis of the individual products of iodination in cyclohexane resulted in rather high insertion into non-activated CH bonds, without noticeable loss of iodine. Syntheses of new phospholipid and ganglioside membrane probes are also described which incorporate the Dcp function via a labile ester bond. A [125I]-Dcp-phosphatidylcholine probe exhibiting high specific radioactivity (~500 Ci mmol-1) was easily prepared at yields of 90% (on the starting Na125I), by using peracetic acid as an oxidant. Furthermore, it was successfully used for photolabelling of the integral protein hemagglutinin in a well-characterised influenza virus model. In summary, the Dcp group is efficient for labelling a wide variety of molecules, and as such, it provides a new tool for exploring a diverse range of biological systems.
- Vodovozova, Elena L.,Tsibizova, Ekaterina V.,Molotkovsky, Julian G.
-
p. 2221 - 2228
(2007/10/03)
-
- Regioselective synthesis of (+)-S-2-amino-5-iodoacetamidopentanoic and (+)-S-2-amino-6-iodoacetamidohexanoic acids
-
Mild reaction conditions were developed for the preparation of the active-site-directed irreversible enzyme inhibitors (+)-S-2-amino-5-iodoacetamido-pentanoic acid and (+)-S-2-amino-6-iodoacetamido-hexanoic acid.
- Trujillo,Ceballos,Yanez,Joseph-Nathan
-
p. 683 - 691
(2007/10/02)
-
- Acyl Substituent Effects on Rates of Acyl Transfer to Thiolate, Hydroxide, and Oxy Dianions
-
The rates of transfer of a series of polar aliphatic acyl groups (-0.3 (*) (*) (*) 1.05) from p-nitrophenol to hydroxide, to the thiol anion of N-acetyl-L-cysteine, and to a series of phosphonate dianions have been determined in aqueous solution.The rate constants for the alkaline hydrolysis of ten p-nitrophenyl esters can be correlated reasonably well (r = 0.981) to the single-parameter Hammett-Taft equation based on the polar substituent constant.The reaction constant for the alkaline hydrolysis is (*) = 2.9 with an interval estimator (90percent confidence) of +/-0.3.The (*) value for the thiolysis reaction is only slightly larger (16 +/- 13percent) than the corresponding value for the alkaline hydrolysis reaction.These kinetic (*) values are essentially identical with the equlibrium (*) for hydroxide or thiolate addition to aldehydes (Kanchuger and Byers).To the extent that gem diolate and thiohemiacetalate formation are appropriate model reactions for the formation of the anionic tetrahedral intermediates in the corresponding acyl transfer reactions, the magnitude of the kinetic (*) values suggests that the transition states for the alkaline hydrolysis and for the thiolysis reactions are similar, in geometry and charge distribution, to the intermediates.Acyl transfer from p-nitrophenol to phosphonate dianions involves an uncatalyzed nucleophilic displacement by the oxy dianion.The (*) value for the reaction of (chloromethyl)phosphonate with the p-nitrophenyl esters is 2.4 (+/-0.3).The second-order rate constants for the reactions between the phosphonates and p-nitrophenyl acetate, p-nitrophenyl chloroacetate, and p-nitrothiophenyl acetate show a small sensitivity to the basicity (pKa2) of the nucleophile (βnuc ca. 0.3).An explanation of the magnitudes of the (*) and βnuc values, and of the anomalously low reaction rates (relative to oxy monoanions and amines of comparable basicities) for acyl transfer to the phosphonates, is that electrostatic interactions and desolvation of the oxy dianion make substantial contributions to the activation energy barrier for nucleophilic attack.
- Shames, Spencer L.,Byers, Larry D.
-
p. 6170 - 6177
(2007/10/02)
-