1612868-08-2Relevant academic research and scientific papers
Linear aliphatic dialkynes as alternative linkers for double-click stapling of p53-derived peptides
Lau, Yu Heng,De Andrade, Peterson,McKenzie, Grahame J.,Venkitaraman, Ashok R.,Spring, David R.
, p. 2680 - 2683 (2014)
We investigated linear aliphatic dialkynes as a new structural class of i,i+7 linkers for the double-click stapling of p53-based peptides. The optimal combination of azido amino acids and dialkynyl linker length for MDM2 binding was determined. In a direct comparison between aliphatic and aromatic staple scaffolds, the aliphatic staples resulted in superior binding to MDM2 in vitro and superior p53-activating capability in cells when using a diazidopeptide derived from phage display. This work demonstrates that the nature of the staple scaffold is an important factor that can affect peptide bioactivity in cells.
