Solid-Phase Synthesis of Lipidated Ras Peptides Employing the Ellman Sulfonamide Linker

A detailed study on the solid-phase synthesis of lipidated peptides of the Ras family employing the Ellman sulfonamide linker is reported. Using the C-terminal N-Ras sequence, critical issues such as lipidated amino acid resin loading, peptide elongation in the presence of labile groups and optimized conditions for release of the peptides were investigated. A versatile methodology for the synthesis of peptides with diverse lipid motifs and C-terminal methyl esters has accordingly been established

Mobile decision support for transplantation patient data

In high-critical medical fields instant information delivery is essential. Task-flow analyses within the transplantation unit of the Technische Universität München revealed that valuable time could be saved in pre-transplantation management being able to retrieve data of organ receivers ubiquitously. Inspired by this clinical scenario, a mobile application was designed and implemented providing surgeons with decision-relevant information on potential organ receivers. It assists them in considering the prospects of forthcoming organ transplantations and facilitates decision making and documentation with regard to high security demands. The described system services three organ receiver lists and is used by the surgeons in every transplantation procedure. After a 6-month period of clinical usage, the system has been evaluated in terms of handling, clinical benefit and total time savings. Intuitive, ubiquitous access to decision-relevant patient data and authenticated documentation were the major improvements with average total time savings of 50 min in comparison to the old system

PDA-based decision support and documentation for transplantation surgery data

The Transplantation Unit of the Technical University of Munich has developed a mobile, handheld based application for preoperative transplantation patient management. It provides information on potential organ receivers and thus assists the surgeons in considering the prospects of a forthcoming organ transplantation. Any decision is documented and authenticated. The system employs sophisticated security mechanisms for both the front-ends and the synchronization conduit

Small-molecule inhibition of APT1 affects Ras localization and signaling

Cycles of depalmitoylation and repalmitoylation critically control the steady-state localization and function of various peripheral membrane proteins, such as Ras proto-oncogene products. Interference with acylation using small molecules is a strategy to modulate cellular localization—and thereby unregulated signaling—caused by palmitoylated Ras proteins. We present the knowledge-based development and characterization of a potent inhibitor of acyl protein thioesterase 1 (APT1), a bona fide depalmitoylating enzyme that is, so far, poorly characterized in cells. The inhibitor, palmostatin B, perturbs the cellular acylation cycle at the level of depalmitoylation and thereby causes a loss of the precise steady-state localization of palmitoylated Ras. As a consequence, palmostatin B induces partial phenotypic reversion in oncogenic HRasG12V-transformed fibroblasts. We identify APT1 as one of the thioesterases in the acylation cycle and show that this protein is a cellular target of the inhibitor