Dephosphorylation of D-peptide derivatives to form biofunctional, supramolecular nanofibers/hydrogels and their potential applications for intracellular imaging and intratumoral chemotherapy

J Am Chem Soc. 2013 Jul 3;135(26):9907-14. doi: 10.1021/ja404215g. Epub 2013 Jun 21.


D-Peptides, as the enantiomers of the naturally occurring L-peptides, usually resist endogenous proteases and are presumably insensitive to most enzymes. But, it is unclear whether or how a phosphatase catalyzes the dephosphorylation from D-peptides. In this work, we examine the formation of the nanofibers of D-peptides via enzymatic dephosphorylation. By comparing the enzymatic hydrogelation of L-peptide and D-peptide based hydrogelators, we find that the chirality of the precursors of the hydrogelators affects little on the enzymatic hydrogelation resulted from the removal of the phosphate group from a tyrosine phosphate residue. The attachment of a therapeutic agent (e.g., taxol) or a fluorophore (e.g., 4-nitro-2,1,3-benzoxadiazole) to the D-peptide based hydrogelators affords a new type of biostable or biocompatible hydrogelators, which may find applications in intratumoral chemotherapy or intracellular imaging, respectively. This work, as the first comprehensive and systematic study of the unexpected enzymatic dephosphorylation of D-peptides, illustrates a useful approach to generate supramolecular hydrogels that have both biostability and other desired functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / pharmacology
  • Molecular Structure
  • Nanofibers* / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Phosphorylation
  • Structure-Activity Relationship


  • Hydrogels
  • Macromolecular Substances
  • Peptides