Design of new acid-activated cell-penetrating peptides for tumor drug delivery.

ABSTRACT: TH(AGYLLGHINLHHLAHL(Aib)HHIL-NH₂), a histidine-rich, cell-penetrating peptide with acid-activated pH response, designed and synthesized by our group, can effectively target tumor tissues with an acidic extracellular environment. Since the protonating effect of histidine plays a critical role in the acid-activated, cell-penetrating ability of TH, we designed a series of new histidine substituents by introducing electron donating groups (Ethyl, Isopropyl, Butyl) to the C-2 position of histidine. This resulted in an enhanced pH-response and improved the application of TH in tumor-targeted delivery systems. The substituents were further utilized to form the corresponding TH analogs (Ethyl-TH, Isopropyl-TH and Butyl-TH), making them easier to protonate for positive charge in acidic t

SUBMITTER: Yao J 

PROVIDER: S-EPMC5465999 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature