Helical peptide models for protein glycation: proximity effects in catalysis of the Amadori rearrangement.

INTRODUCTION: Non-enzymatic glycation of proteins has been implicated in various diabetic complications and age-related disorders. Proteins undergo glycation at the N-terminus or at the epsilon-amino group of lysine residues. The observation that only a fraction of all lysine residues undergo glycation indicates the role of the immediate chemical environment in the glycation reaction. Here we have constructed helical peptide models, which juxtapose lysine with potentially catalytic residues in order to probe their roles in the individual steps of the glycation reaction. RESULTS: The peptides investigated in this study are constrained to adopt helical conformations allowing residues in the i and i+4 positions to come into spatial proximity, while residues i and i+2 are far apart. The placing of aspartic acid and histidine residues at interacting positions with lysine modulates the steps involved in early peptide glycation (reversible Schiff base formation and its subsequent irreversible conversion to a ketoamine product, the Amadori rearrangement). Proximal positioning of aspartic acid or histidine with respect to the reactive lysine residue retards initial Schiff base formation. On the contrary, aspartic acid promotes catalysis of the Amadori rearrangement. Presence of the strongly basic residue arginine proximate to lysine favorably affects the pK(a) of both the lysine epsilon-amino group and the singly glycated lysine, aiding in the formation of doubly glycated species. The Amadori product also formed carboxymethyl lysine, an advanced glycation endproduct (AGE), in a time-dependent manner. CONCLUSIONS: Stereochemically defined peptide scaffolds are convenient tools for studying near neighbor effects on the reactivity of functional amino acid sidechains. The present study utilizes stereochemically defined peptide helices to effectively demonstrate that aspartic acid is an efficient catalytic residue in the Amadori arrangement. The results emphasize the structural determinants of Schiff base and Amadori product formation in the final accumulation of glycated peptides.     

Determination of alpha activity ratios by alpha spectrometry in the presence of large amounts of uranium

A direct evaporation method is described for the preparation of sources using stainless steel as the backing material and tetraethylene glycol (TEG) as a spreading agent in the presence of large amounts of uranium. It is shown that FWHM and tail contribution at the low energy peak due to energy degradation of the high energy peak can be optimized by heating the source under controlled conditions in a furnace at 500–600°C for about 15 min. An accuracy of 0.5–1% is demonstrated for the determination of²³⁸Pu/(²³⁹Pu+²⁴⁰Pu) alpha activity ratio in the U/Pu range of 10 to 1500 generally encountered in dissolver solution of irradiated fuel.     

A random 1-011-011-01algorithm for depth first search

In this paper we present a fast parallel algorithm for constructing a depth first search tree for an undirected graph. The algorithm is anRNC algorithm, meaning that it is a probabilistic algorithm that runs in polylog time using a polynomial number of processors on aP-RAM. The run time of the algorithm isO(T _MM(n) log³ n), and the number of processors used isP _MM (n) whereT _MM(n) andP _MM(n) are the time and number of processors needed to find a minimum weight perfect matching on ann vertex graph with maximum edge weightn.This research was done while the first author was visiting the Mathematical Research Institute in Berkeley. Research supported in part by NSF grant 8120790.Supported by Air Force Grant AFOSR-85-0203A.     

Event-by-event search for charged-neutral fluctuations in Pb-Pb collisions at 158 A⋅GeV

We analyse the proton electromagnetic form factor ratioR(Q ² ) =QF ₂ (Q ² )/F ₁ (Q ² ) as a function of momentum transferQ ² within perturbative QCD. We find that the prediction for (R(Q ² ) at large momentum transferQ depends on the exclusive quark wave functions, which are unknown. For a wide range of wave functions we find thatQF ₂ F ₁ ～ const. at large momentum transfer, which is in agreement with recent JLAB data.     

Preparation and characterization of heterobimetallic tetraxanthates and their complexes with Lewis bases

Some new heterobimetallic tetraxanthates of the type M[Ag(Etxant)₂]₂ [M = Co(II) or Ni(II), Etxant = ethylxanthate] and their complexes of general formula M[Ag(Etxant)₂]₂.xL [x = 2 when L= dimethylsulphoxide (DMSO), triphenylphosphine (Pph₃), pyridine(py) or 2-aminopyridine (2-ampy); x = 3 when L = 2,2′-bipyridine (bipy)] have been prepared and characterized by elemental analysis, molar conductance, magnetic susceptibility, infrared and electronic spectral studies. Magnetic and electronic spectral studies indicate square planar geometry around Ni(II) and Co(II) in heterobimetallic tetraxanthates and Ni[Ag(Etxant)₂]₂.2PPh₃ and octahedral geometry around the above metal ions in the remaining complexes.     

Local particle densities and global multiplicities in central heavy ion interactions at 3.7, 14.6, 60 and 200A GeV

The energy and centrality dependence of local particle pseudorapidity densities as well as validity of various parametrizations of the distributions are examined. The dispersion, , of the rapidity density distribution of produced particles varies slowly with centrality and is 0.80, 0.98, 1.21 and 1.41 for central interactions at 3.7, 14.6, 60 and 200A GeV incident energy, respectively, is found to be independent of the size of the interacting system at fixed energy. A novel way of representing the window dependence of the multiplicity as normalized variance versus inverse average multiplicity is outlined.