P3 and P4 position analysis of vinyl ester pseudopeptide proteasome inhibitors

Here following is the report on the use of small, focused libraries to study P3 and P4 positions of vinyl ester pseudopeptides, selective inhibitors for trypsin-like activity of the 20S proteasome. Two small libraries of tripeptidic-based vinyl ester derivative proteasome inhibitors were synthesized...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-06, Vol.16 (12), p.3125-3130
Main Authors: Marastoni, Mauro, Baldisserotto, Anna, Trapella, Claudio, Gavioli, Riccardo, Tomatis, Roberto
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biological and medical sciences
Esters - chemistry
Medical sciences
Miscellaneous
Peptides - chemical synthesis
Peptides - chemistry
Peptides - pharmacology
Pharmacology. Drug treatments
Proteasome Endopeptidase Complex - metabolism
Proteasome Inhibitors
Small libraries
Solid-phase synthesis
Trypsin-like activity
Vinyl Compounds - chemistry
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Summary:Here following is the report on the use of small, focused libraries to study P3 and P4 positions of vinyl ester pseudopeptides, selective inhibitors for trypsin-like activity of the 20S proteasome. Two small libraries of tripeptidic-based vinyl ester derivative proteasome inhibitors were synthesized and tested, starting with the Hmb-Val-Gln-Leu-VE prototype. The P3 and P4 positions were investigated with a complete set of amino acid residues, some of which showed remarkable selective inhibition of the trypsin-like (β2) subunit. In both positions, aromatic and hydrophobic residues were preferred.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.03.070