477254-82-3Relevant academic research and scientific papers
Tailored Peptide Phenyl Esters Block ClpXP Proteolysis by an Unusual Breakdown into a Heptamer–Hexamer Assembly
Lakemeyer, Markus,Bertosin, Eva,M?ller, Friederike,Balogh, Dóra,Strasser, Ralf,Dietz, Hendrik,Sieber, Stephan A.
, p. 7127 - 7132 (2019)
The proteolytic complex ClpXP is fundamental to bacterial homeostasis and pathogenesis. Because of its conformational flexibility, the development of potent ClpXP inhibitors is challenging, and novel tools to decipher its intricate regulation are urgently needed. Herein, we present amino acid based phenyl esters as molecular probes to study the activity and oligomerization of the ClpXP complex of S. aureus. Systematic screening of (R)- and (S)-amino acids led to compounds showing potent inhibition, as well as stimulation of ClpXP-mediated proteolysis. Substoichiometric binding of probes arrested ClpXP in an unprecedented heptamer–hexamer assembly, in which the two heptameric ClpP rings are dissociated from each other. At the same time, the affinity between ClpX and ClpP increased, leading to inhibition of both enzymes. This conformational arrest is beneficial for the consolidated shutdown of ClpXP, as well as for the study of the oligomeric state during its catalytic cycle.
An efficient synthesis of l-3,4,5-trioxygenated phenylalanine compounds from l-tyrosine
Chen, Ruijiao,Liu, Hao,Liu, Xiubing,Chen, Xiaochuan
, p. 3565 - 3570 (2013/04/24)
A new strategy for the synthesis of l-3,4,5-trioxygenated phenylalanine derivatives from l-tyrosine is developed for the first time. The approach, featuring the transformation of aryl diiodide to bis-phenol via a one-pot procedure including lithiation, boronation, and oxidation, is highly practical. By this robust protocol, N-protected l-3,5-bis(tert-butyldimethylsilyloxy)-4- methoxy-phenylalanine and l-3,4,5-trimethoxy-phenylalanine derivatives were obtained from l-tyrosine in 9 steps with 36-40% overall yields.
Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design
Furet, Pascal,Imbach, Patricia,Noorani, Maria,Koeppler, Juergen,Laumen, Kurt,Lang, Marc,Guagnano, Vito,Fuerst, Peter,Roesel, Johannes,Zimmermann, Johann,García-Echeverría, Carlos
, p. 4810 - 4813 (2007/10/03)
Proteasome inhibition is a therapeutic concept of current interest in anticancer research. We report here the design, synthesis, and biological characterization of prototypes of a new class of noncovalent proteasome inhibitors showing high activity in bio
