NPE-caged-proton

Time-resolved infrared spectroscopy of pH-induced aggregation of the Alzheimer Abeta(1-28) peptide.[Pubmed:18462754]

J Mol Biol. 2008 Jun 6;379(3):589-96.

Aggregation of the Alzheimer's disease-related Abeta(1-28) peptide was induced by a rapid, sub-millisecond pH jump and monitored by time-resolved infrared spectroscopy on the millisecond to second time-scale. The release of protons was induced by the photolysis of a caged compound, 1-(2-nitrophenyl)ethyl sulfate (NPE-sulfate). The pH jump generated in our experimental setup is used to model the Abeta peptide structural conversions that may occur in the acidic endosomal/lysosomal cell compartment system. The aggregation of the Abeta(1-28) peptide induced by the pH jump from 8.5 to <6 yields an antiparallel beta-sheet structure. The kinetics of the structural transition is biphasic, showing an initial rapid phase with a transition from random coil to an oligomeric beta-sheet form with a time constant of 3.6 s. This phase is followed by a second slower transition, which yields larger aggregates during 48.0 s.

Kinetics of proton release after flash photolysis of 1-(2-nitrophenyl)ethyl sulfate (caged sulfate) in aqueous solution.[Pubmed:15998092]

J Am Chem Soc. 2005 Jul 13;127(27):9865-74.

The kinetics of proton release after laser photolysis of 1-(2-nitrophenyl)ethyl sulfate (caged sulfate) have been characterized by time-resolved absorbance and photoacoustic methods. The absorbance at approximately 400 nm is observed to rise with a biphasic behavior in which a prompt component (formation of the nitronic acid) is followed by a slower (tau approximately 63 +/- 6 ns) phase (deprotonation of the nitronic acid). The decay of this intermediate occurs with a lifetime which is affected by the pH of the solution and the laser pulse energy. In buffered aqueous solution at pH 7, 20 degrees C the aci-nitro decay rate is 18 +/- 4 s(-1). Protons are released to the solution with rate (1.58 +/- 0.09) x 10(7) s(-1) at neutral pH from the nitronic acid intermediate. From the numerical analysis of the protonation kinetics of suitable pH indicators, we could estimate the pK(a) of the nitronic acid as 3.69 +/- 0.05. At acidic pH, a substantial fraction of the aci-nitro intermediate is in the protonated form and this leads to a biphasic release of protons, with the slower phase being characterized by an apparent rate constant strongly dependent on the pH. The strongly acidic character of the final photoproduct (sulfate ion) means that there is negligible buffering of photoreleased protons.

Characterization of a new caged proton capable of inducing large pH jumps.[Pubmed:12414718]

Biophys J. 2002 Nov;83(5):2864-71.

A new caged proton, 1-(2-nitrophenyl)ethyl sulfate (caged sulfate), is characterized by infrared spectroscopy and compared with a known caged, proton 2-hydroxyphenyl 1-(2-nitrophenyl)ethyl phosphate (caged HPP). In contrast to caged HPP, caged sulfate can induce large pH jumps and protonate groups that have pK values as low as 2.2. The photolysis mechanism of caged sulfate is analogous to that of P(3)-[1-(2-nitrophenyl)ethyl] ATP (caged ATP), and the photolysis efficiency is similar. The utility of this new caged compound for biological studies was demonstrated by its ability to drive the acid-induced conformational change of metmyoglobin. This transition from the native conformation to a partially unfolded form takes place near pH 4 and was monitored by near-UV absorption spectroscopy.