TY - JOUR
T1 - Elucidation of the α-keto-aldehyde binding mechanism
T2 - A lead structure motif for proteasome inhibition
AU - Gallastegui, Nerea
AU - Stein, Martin
AU - Schmidt, Boris
AU - Kloetzel, Peter Michael
AU - Huber, Robert
AU - Groll, Michael
PY - 2011/1/10
Y1 - 2011/1/10
N2 - Lead role: The role of peptidyl α-keto aldehydes as proteasome inhibitors is well established, yet their molecular binding mode requires additional investigation (see picture). A cyclization mechanism that proceeds through hemiketal and Schiff base formation with the nucleophilic N-terminal threonine of β5 is shown to result in the reversible formation of a 5,6-dihydro-2H-1,4-oxazine ring. This agent serves as a new lead for the development of anticancer drugs.
AB - Lead role: The role of peptidyl α-keto aldehydes as proteasome inhibitors is well established, yet their molecular binding mode requires additional investigation (see picture). A cyclization mechanism that proceeds through hemiketal and Schiff base formation with the nucleophilic N-terminal threonine of β5 is shown to result in the reversible formation of a 5,6-dihydro-2H-1,4-oxazine ring. This agent serves as a new lead for the development of anticancer drugs.
KW - drug discovery
KW - peptidyl glyoxals
KW - proteasomes
KW - reversible inhibition
KW - structure elucidation
UR - http://www.scopus.com/inward/record.url?scp=78650904648&partnerID=8YFLogxK
U2 - 10.1002/anie.201005488
DO - 10.1002/anie.201005488
M3 - Article
C2 - 21154547
AN - SCOPUS:78650904648
SN - 1433-7851
VL - 50
SP - 542
EP - 544
JO - Angewandte Chemie International Edition in English
JF - Angewandte Chemie International Edition in English
IS - 2
ER -