Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

…, N Vartak, A Chandra, M Hoffmann, SA Hahn, G Triola… - Nature, 2013 - nature.com
The KRAS oncogene product is considered a major target in anticancer drug discovery 1, 2,
3. However, direct interference with KRAS signalling has not yet led to clinically useful drugs
3, 4, 5, 6, 7, 8. Correct localization and signalling by farnesylated KRAS is regulated by the …

Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo

…, A Chandra, M Bierbaum, L Gremer, G Triola… - Nature chemical …, 2011 - nature.com
Abstract Lipidated Rho and Rab GTP-binding proteins are transported between membranes
in complex with solubilizing factors called'guanine nucleotide dissociation inhibitors'(GDIs).
Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but …

Bioorthogonal chemistry for site-specific labeling and surface immobilization of proteins

YX Chen, G Triola, H Waldmann - Accounts of chemical research, 2011 - ACS Publications
Understanding protein structure and function is essential for uncovering the secrets of
biology, but it remains extremely challenging because of the high complexity of protein
networks and their wiring. The daunting task of elucidating these interconnections requires …

Influence of the lipidation motif on the partitioning and association of N-Ras in model membrane subdomains

K Weise, G Triola, L Brunsveld… - Journal of the …, 2009 - ACS Publications
In a combined chemical biological and biophysical approach using time-lapse tapping-
mode atomic force microscopy, we studied the partitioning of differently lipidated N-Ras
proteins with various membrane-localization motifs into lipid domains of canonical model raft …

Identification of acyl protein thioesterases 1 and 2 as the cellular targets of the Ras‐signaling modulators palmostatin B and M

…, FJ Dekker, K Görmer, G Triola… - Angewandte Chemie …, 2011 - Wiley Online Library
Cellular proteome labeling profile for probes 3 and 4 derived from palmostatin M after 20 min
incubation at various probe concentrations (50, 10, 1 μM). A) Fluorescent gel highlighting three
major bands corresponding to PPT1 (34.193 kDa), APT1 (MW=24.67 kDa), and APT2 (MW=24.73 …

Membrane-mediated induction and sorting of K-Ras microdomain signaling platforms

…, J Nikolaus, N Opitz, S Koch, G Triola… - Journal of the …, 2010 - ACS Publications
The K-Ras4B GTPase is a major oncoprotein whose sig-naling activity depends on its
correct localization to negatively charged subcellular membranes and nanoclustering in
membrane microdomains. Selective localization and clustering are mediated by the …

[HTML][HTML] N-Ras forms dimers at POPC membranes

…, T Rudack, P Bachler, D Mann, G Triola… - Biophysical journal, 2012 - Elsevier
Ras is a central regulator of cellular signaling pathways. It is mutated in 20–30% of human
tumors. To perform its function, Ras has to be bound to a membrane by a posttranslationally
attached lipid anchor. Surprisingly, we identified here dimerization of membrane anchored …

Revealing conformational substates of lipidated N-Ras protein by pressure modulation

S Kapoor, G Triola, IR Vetter… - Proceedings of the …, 2012 - National Acad Sciences
Regulation of protein function is often linked to a conformational switch triggered by
chemical or physical signals. To evaluate such conformational changes and to elucidate the
underlying molecular mechanisms of subsequent protein function, experimental …

Synthesis of cyclopropene analogues of ceramide and their effect on dihydroceramide desaturase

G Triola, G Fabriàs, J Casas… - The Journal of organic …, 2003 - ACS Publications
The synthesis of several analogues of the N-[(1 R, 2 S)-2-hydroxy-1-hydroxymethyl-2-(2-
tridecyl-1-cyclopropenyl) ethyl] octanamide (GT11), the first reported inhibitor of
dihydroceramide desaturase, as well as their effects on this enzyme, are described …

A highly efficient strategy for modification of proteins at the C terminus

L Yi, H Sun, YW Wu, G Triola… - Angewandte Chemie …, 2010 - Wiley Online Library
A new linker: In a facile, chemoselective, and potentially general method for protein
modification at the C terminus oxyamino‐modified proteins obtained from protein thioesters
react rapidly with ketones under mild conditions. This strategy was used for fluorescence …