The natural product hybrid of Syringolin A and Glidobactin A synergizes proteasome inhibition potency with subsite selectivity.
The preparation of a Syringolin A/Glidobactin A hybrid (SylA-GlbA) consisting of a SylA macrocycle connected to the GlbA side chain and its potent proteasome targeting of all three proteasomal subsites is reported. The influence of the syrbactin macrocycle moiety on subsite selectivity is demonstrated.
Clerc
Jérôme
J
Zentrum für Medizinische Biotechnologie, Fakultät für Biologie und Geographie, Universität Duisburg-Essen, 45117 Essen, Germany.
Li
Nan
N
Krahn
Daniel
D
Groll
Michael
M
Bachmann
André S
AS
Florea
Bogdan I
BI
Overkleeft
Herman S
HS
Kaiser
Markus
M
D001665:Binding Sites / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D001688:Biological Products; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; C407267:syringolin A; C057878:glidobactin A