Ontology highlight
ABSTRACT:
SUBMITTER: Onyango JO
PROVIDER: S-EPMC4427346 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Angewandte Chemie (International ed. in English) 20150204 12
The pH low insertion peptide (pHLIP) offers the potential to deliver drugs selectively to the cytoplasm of cancer cells based on tumor acidosis. The WT pHLIP inserts into membranes with a pH50 of 6.1, while most solid tumors have extracellular pH (pH(e)) of 6.5-7.0. To close this gap, a SAR study was carried out to search for pHLIP variants with improved pH response. Replacing Asp25 with α-aminoadipic acid (Aad) adjusts the pH50 to 6.74, matching average tumor acidity, and replacing Asp14 with γ ...[more]