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Background. Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. Methods. We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed byatreatment switch. We adjusted for patients’ characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. Results. A total of 81738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/µL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997–1998 to 9.7% in 2009–2011 (P

13C NMR spectral data are presented for a variety of possible neuropeptides composed of L-Asp, Ac-L-Asp, and L-Glu which contain alpha and beta peptide linkages. The data for the various compounds are compared to the data presented for Ac-Asp-Glu, a known neuropeptide, in order to gain structural information about the related compounds. Indications are that for compounds 1 and 5, the cis peptide bond configuration exists due to the interaction of zwitterionic species. This interaction appears to be eliminated when the beta peptide bonds are formed, as in the case of compounds 3 and 7. Spin-lattice relaxation times were used to confirm the structures. Electron-nuclear relaxation rates are also used to elucidate the metal ion binding sites of these species.

Fudaa is an open-source, object oriented and distributed framework dedicated to the integration of scientific simulation code in homogeneous, graphic, and communicating interfaces. This tool, developed in Java and Corba, provides a user-friendly, common, and stable environment for independent simulation codes. Whereas in most cases simulation codes exchange data only through files, with Fudaa, they are used as distributed software components that can communicate with each other through the network using a common data model. Moreover, they benefit from an efficient and homogenous graphic interface which can integrate numerous developments available on the Internet thanks to the GPL license. Today, Fudaa is evolving to provide geographic information system features and integration in a Web and service-oriented environment.

Several phosphoserine, phosphothreonine and phosphotyrosine synthons suitable for the stepwise synthesis of phosphopeptides were prepared. Treatment of methylthiomethyl (MTM) esters of either Z-, Boc-, Allocserine and threonine with phosphochloridate in pyridine followed by MgBr2 cleavage of MTM in diethyl ether afforded the title compounds in good yield. Thiophosphoserine and phosphotyrosine synthons were also obtained by the phosphoramidite method using di-(2,2,2-trichloroethyl)-N,N-diisopropylphosphoramidite and MCPBA as oxidizing reagent. Trichloroethyl proved valuable as phosphate protecting group especially in phosphotyrosine derivatives owing to its stability in acidic conditions. These synthons were involved in the liquid-phase synthesis of several phospho and/or thiophosphopeptides related to either src-protein kinase or rat liver pyruvate kinase.

In this paper, we report the solid-phase synthesis of peptides containing O-phosphonoserine using BOP as coupling reagent. Commercially available Fmoc amino-acids linked to p-alkoxybenzyl resin were used in the first step and Alloc amino acids in the following. Alloc group was removed by catalytic hydrostannolytic cleavage. Acid-labile side-chain protecting groups (including phosphate residue) were used. Thus, both removal of side-chain protecting groups and cleavage of the phosphopeptide from the resin were achieved in one step by treatment with TFA. Alloc serine was phosphorylated by the phosphoramidite method. This strategy enables the preparation of peptides with selectively phosphorylated residue and overcomes problems due to repetitive treatments with TFA and final cleavage with HF.

In this paper, we report the solid-phase synthesis of peptides containing O-phosphonoserine using BOP as coupling reagent. Commercially available Fmoc amino-acids linked to p-alkoxybenzyl resin were used in the first step and Alloc amino acids in the following. Alloc group was removed by catalytic hydrostannolytic cleavage. Acid-labile side-chain protecting groups (including phosphate residue) were used. Thus, both removal of side-chain protecting groups and cleavage of the phosphopeptide from the resin were achieved in one step by treatment with TFA. Alloc serine was phosphorylated by the phosphoramidite method. This strategy enables the preparation of peptides with selectively phosphorylated residue and overcomes problems due to repetitive treatments with TFA and final cleavage with HF.

When 2,3,4,6-tetra-O-benzyl-D-glucopyranose, -D-galactopyranose and 2,3,4-tri-O-benzyl-D-xylopyranose were allowed to react in the cold in dichloromethane or acetonitrile as solvent in the presence of trifluoromethanesulfonic (triflic) anhydride, with methyl or benzyl esters of the N-(benzyloxycarbonyl)-L-serine, -L-threonine, and -L-hydroxyproline, an anomeric mixture of the corresponding O-glycosylaminoacids was obtained (55 to 90% overall yield), with the α-anomer being predominant. The same experimental procedure was successfully applied to the condensation of the benzyl ester of the N-(benzyloxycarbonyl)-L-hydroxyproline with 2,3,4-tri-O-benzyl-L-arabinopyranose and 2,3,5-tri-O-benzyl-L-arabinofuranose affording the corresponding condensation products with similar yield. Pure α and β anomers were obtained after column chromatography or crystallization with 30 to 65% yield. Hydrogenolysis of benzyl derivatives afforded the unprotected compounds. Optical rotation, 1H and 13C nmr were the main methods used to assess structure and stereochemistry.

The objective of this study was to determine whether a nonglycosylated portion of glycophorin A (GPA), the main erythrocyte membrane glycoprotein, was involved in the process of invasion of red blood cells (RBC) by merozoites of Plasmodium falciparum, a parasite responsible for the most severe form of malaria. A series of peptides covering the sequence 55-76 situated upstream from the intramembraneous hydrophobic region of GPA was synthesized by an active ester coupling strategy and assessed for invasion-blocking capacity by using an in vitro assay system. Tests showed peptide 65-69, Ala-His-His-Phe-Ser, to be a good inhibitor of the invasion of RBC. Results presented here provide a confirmation of the existence of parasite binding sites on the peptide domain of GPA. Furthermore, comparison of inhibitory activity with peptide composition allowed us to rule out any contribution of a toxic parameter related to hydrophobicity as reported earlier.