Peptide to Peptoid Substitutions Increase Cell Permeability in Cyclic Hexapeptides

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• 作者：Joshua Schwochert ; Rushia Turner ; Melissa Thang ; Ray F Berkeley ; Alexandra R Ponkey ; Kelsie M. Rodriguez ; Siegfried S F Leung ; Bhagyashree Khunte ; Gilles Goetz ; Chris Limberakis ; Amit S. Kalgutkar ; Heather Eng ; Michael J. Shapiro ; Alan M. Mathiowetz ; David A. Price ; Spiros Liras ; Matthew P. Jacobson ; R. Scott Lokey
• 刊名：Organic Letters
• 出版年：2015
• 出版时间：June 19, 2015
• 年：2015
• 卷：17
• 期：12
• 页码：2928-2931
• 全文大小：359K
• ISSN：1523-7052

文摘

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 尾-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.