학술논문
Peptide to Peptoid Substitutions Increase Cell Permeability in Cyclic Hexapeptides.
Document Type
Article
Author
Schwochert, Joshua; Turner, Rushia; Thang, Melissa; Berkeley, Ray F; Ponkey, Alexandra R; Rodriguez, Kelsie M.; Leung, Siegfried S F; Khunte, Bhagyashree; Goetz, Gilles; Limberakis, Chris; Kalgutkar, Amit S.; Eng, Heather; Shapiro, Michael J.; Mathiowetz, Alan M.; Price, David A.; Liras, Spiros; Jacobson, Matthew P.; Lokey, R. Scott
Source
Subject
*PEPTIDES
*SUBSTITUTION reactions
*PERMEABILITY
*CYCLIC compounds
*HEXAPEPTIDES
*CONFORMATIONAL analysis
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Language
ISSN
1523-7060
Abstract
The effect of peptide-to-peptoid substitutions on the passive membrane permeability of an N-methylated cyclic hexapeptide is examined. In general, substitutions maintained permeability but increased conformational heterogeneity. Diversification with nonproteinogenic side chains increased permeability up to 3-fold. Additionally, the conformational impact of peptoid substitutions within a β-turn are explored. Based on these results, the strategic incorporation of peptoid residues into cyclic peptides can maintain or improve cell permeability, while increasing access to diverse side-chain functionality. [ABSTRACT FROM AUTHOR]