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A study was conducted to examine the synthesis of disulfide bonds in endothelin-1 by determining a salt bridge and its possible role in the disulfide bond formation. Distance geometry computations were performed using a HP735 workstation supported by the DIANA program while a SANDER module was utilized to carry out energy minimization and molecular dynamic simulations. Results suggested that the cleavage of Arg52-Cys54 amide bond after the formation of native disulfide bonds.

The conformation of a 23-residue peptide (KR-ET-1), generated by adding the Lys(-2)-Arg(-1) dipeptide to endothelin-1 (ET-1)'s N-terminus, is nearly same as the ET-1 in the carboxylic state and is characterized by a more restricted C-terminal part inclined toward the N-terminus and a well-defined Arg(-1)side chain location in the carboxylate state. KR-ET-1 enhances formation of native disulfide bridges and reduces biological activity that can be attributed to the electrostatic interactions and the Arg(-1)-Glu10 salt bridge.

NaBH4 is used to reduce (5S)-5-alkyl-2, 4-dioxopyrrolidines, which are presumed to be tetramic acids, to yield diastereofacial selectivity in parts when N-replaced analogues are involved. Reduced cis-pyrrolidinores are obtained from carbamate derivatives. The re-face selectivity is increased by enhancing steric inhibition of N-or C-5 replacements. The stereoselectivity is dramatically reversed when the heterobicyclic compound is attenuated. Negligible pyramidalization of the N-atom of the ring is seen by initial measurements, which results in hydride introduction.

The aim of this National Diagnostic and Care Protocol (PNDS) is to explain to the professionals involved the current optimal diagnosis and therapeutic management and care approach for a patient with Takayasu's arteritis. Its purpose is to optimize and harmonize the management and follow-up of this rare disease throughout the country. It also identifies pharmaceutical specialties used in an indication not provided for in the Marketing Authorization, as well as the specialties, products or services necessary for the care of patients but not usually paid for or reimbursed. [ABSTRACT FROM AUTHOR]

Abstract Introduction Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura. Case presentation A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature. Conclusions Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation.

Abstract Background Knottins are small, diverse and stable proteins with important drug design potential. They can be classified in 30 families which cover a wide range of sequences (1621 sequenced), three-dimensional structures (155 solved) and functions (> 10). Inter knottin similarity lies mainly between 15% and 40% sequence identity and 1.5 to 4.5 Å backbone deviations although they all share a tightly knotted disulfide core. This important variability is likely to arise from the highly diverse loops which connect the successive knotted cysteines. The prediction of structural models for all knottin sequences would open new directions for the analysis of interaction sites and to provide a better understanding of the structural and functional organization of proteins sharing this scaffold. Results We have designed an automated modeling procedure for predicting the three-dimensionnal structure of knottins. The different steps of the homology modeling pipeline were carefully optimized relatively to a test set of knottins with known structures: template selection and alignment, extraction of structural constraints and model building, model evaluation and refinement. After optimization, the accuracy of predicted models was shown to lie between 1.50 and 1.96 Å from native structures at 50% and 10% maximum sequence identity levels, respectively. These average model deviations represent an improvement varying between 0.74 and 1.17 Å over a basic homology modeling derived from a unique template. A database of 1621 structural models for all known knottin sequences was generated and is freely accessible from our web server at http://knottin.cbs.cnrs.fr. Models can also be interactively constructed from any knottin sequence using the structure prediction module Knoter1D3D available from our protein analysis toolkit PAT at http://pat.cbs.cnrs.fr. Conclusions This work explores different directions for a systematic homology modeling of a diverse family of protein sequences. In particular, we have shown that the accuracy of the models constructed at a low level of sequence identity can be improved by 1) a careful optimization of the modeling procedure, 2) the combination of multiple structural templates and 3) the use of conserved structural features as modeling restraints.