2 research outputs found
Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells
Deubiquitinating
enzymes play an important role in a plethora of therapeutically relevant
processes and are emerging as pioneering drug targets. Herein, we
present a novel probe, Ubiquitin Specific Protease (USP) inhibitor,
alongside an alkyne-tagged activity-based probe analogue. Activity-based
proteome profiling identified 12 USPs, including USP4, USP16, and
USP33, as inhibitor targets using submicromolar probe concentrations.
This represents the first intact cell activity-based profiling of
deubiquitinating enzymes. Further analysis demonstrated functional
inhibition of USP33 and identified a synergistic relationship in combination
with ATR inhibition, consistent with USP4 inhibition
On multiplicative structure in Quasi-Newton methods for nonlinear equations
We address the problem how additive and multiplicative structure in the derivatives can be exploited for the construction of Quasi-Newton approximations in smooth nonlinear equations. We derive a model algorithm and show its convergence properties based on a Broyden-like update rule. As a consequence of the use of exact multiplicative parts the convergence factor of the q-linear convergence rate is monotonically decreasing with the norm of the multiplicative part at the solution. Moreover, q-superlinear convergence can be shown, if certain compactness properties are valid, and q-quadratic convergence is obtained, if the multiplicative part vanishes at the solutionAvailable from TIB Hannover: RR 1843(92-22) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman