A library approach to the generation of bisubstrate analogue sulfotransferase inhibitors

[reaction: see text]. A library of potential bisubstrate analogue inhibitors (1) targeting sulfotransferase enzymes was generated by the chemoselective ligation of the PAPS mimic 2 with a panel of 447 aldehydes. Preliminary screening has identified compounds that inhibit estrogen sulfotransferase (EST), an enzyme relevant to breast cancer.     

Comparative analysis of different computer handling systems for gamma-spectrometric data developed at C.C.R. Ispra

Three different computer systems for gamma-spectrometric data-handling have been developed at the Joint Nuclear Research Center of Ispra. The systems are: (1) batchwise treatment of the data with a large computer, (2) time-shared teleprocessing by means of a centralised computer, (3) use of a small computer at the laboratory site. The paper describes both hardware and software of the three systems with emphasis on their practical use and on advantages and disadvantages in routine application. A partial analysis of the running costs of the systems is also presented.     

Lp theory for the multidimensional aggregation equation

We consider well‐posedness of the aggregation equation ∂_tu + div(uv) = 0, v = −▿K * u with initial data in \input amssym ${\cal P}_2 {\rm (\Bbb R}^d {\rm )} \cap L^p ({\Bbb R}^d )$ in dimensions 2 and higher. We consider radially symmetric kernels where the singularity at the origin is of order |x|^α, α > 2 − d, and prove local well‐posedness in \input amssym ${\cal P}_2 { (\Bbb R}^d {\rm )} \cap L^p ({\Bbb R}^d )$ for sufficiently large p < p_s. In the special case of K(x) = |x|, the exponent p_s = d/(d = 1) is sharp for local well‐posedness in that solutions can instantaneously concentrate mass for initial data in \input amssym ${\cal P}_2 { (\Bbb R}^d {\rm )} \cap L^p ({\Bbb R}^d )$ with p < p_s. We also give an Osgood condition on the potential K(x) that guarantees global existence and uniqueness in \input amssym ${\cal P}_2 { (\Bbb R}^d {\rm )} \cap L^p ({\Bbb R}^d )$ . © 2010 Wiley Periodicals, Inc.     

Chemoselective elaboration of O-linked glycopeptide mimetics by alkylation of 3-thioGalNAc.

A critical branch point in mucin-type oligosaccharides is the beta 1-->3 glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. We report here a strategy for the synthesis of O-linked glycopeptide analogues that replaces this linkage with a thioether amenable to construction by chemoselective ligation. The key building block was a 2-azido-3-thiogalactose-Thr analogue that was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. Higher order oligosaccharides were readily generated by alkylation of the corresponding 3-thioGalNAc with N-bromoacetamido sugars. The rapid assembly of "core 1"and "core 3" O-linked glycopeptide mimetics was accomplished in this fashion.