In:
Angewandte Chemie, Wiley, Vol. 129, No. 6 ( 2017-02), p. 1547-1551
Abstract:
Therapeutic applications of peptides are currently limited by their proteolytic instability and impermeability to the cell membrane. A general, reversible bicyclization strategy is now reported to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell‐penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell‐permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell‐permeable bicyclic peptidyl inhibitor against the NEMO‐IKK interaction.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.201610888
Language:
English
Publisher:
Wiley
Publication Date:
2017
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