Abstract:
:Several diseases, such as cancer, are characterized by acidification of the extracellular environment. Acidosis can be employed as a target to specifically direct therapies to the diseased tissue. We have used first principles to design an acidity-triggered rational membrane (ATRAM) peptide with high solubility in solution that is able to interact with lipid membranes in a pH-dependent fashion. Biophysical studies show that the ATRAM peptide binds to the surface of lipid membranes at pH 8.0. However, acidification leads to the peptide inserting into the lipid bilayer as a transmembrane α-helix. The insertion of ATRAM into membranes occurs at a moderately acidic pH (with a pK of 6.5), similar to the extracellular pH found in solid tumors. Studies with human cell lines showed a highly efficient pH-dependent membrane targeting, without causing toxicity. Here we show that it is possible to rationally design a soluble peptide that selectively targets cell membranes in acidic environments.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Nguyen VP,Alves DS,Scott HL,Davis FL,Barrera FNdoi
10.1021/acs.biochem.5b00856subject
Has Abstractpub_date
2015-11-03 00:00:00pages
6567-75issue
43eissn
0006-2960issn
1520-4995journal_volume
54pub_type
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