In:
European Journal of Organic Chemistry, Wiley, Vol. 2017, No. 39 ( 2017-10-25), p. 5921-5934
Abstract:
Most known β2‐selective proteasome inhibitors suffer from relatively poor cell permeability as the result of a net positive charge caused by the basic moiety at P1. In this paper, we describe the synthesis of oligopeptide vinyl sulfones that contain different amino acids bearing amino groups with reduced basicity at P1 and/or P3. For this, we developed the first enantioselective synthesis of lysine(4‐ene) and lysine(4‐yne). These amino acids, as well as histidine and diaminopropionic‐acid‐glycine, were incorporated at the P1 and/or P3 positions of oligopeptide vinyl sulfones. All inhibitors were found to inhibit β2, but with a loss of potency compared to our most potent and selective β2 inhibitor, LU‐102. These results notwithstanding, our results provide important insights for the future design of β2‐selective proteasome inhibitors.
Type of Medium:
Online Resource
ISSN:
1434-193X
,
1099-0690
DOI:
10.1002/ejoc.v2017.39
DOI:
10.1002/ejoc.201701174
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
1475010-7
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