Roles of key residues and lipid dynamics reveal pHLIP-membrane interactions at intermediate pH.

ABSTRACT: The pH-low insertion peptide (pHLIP) and its analogs sense the microenvironmental pH variations in tumorous cells and serve as useful anticancer drug deliveries. The pHLIP binds peripherally to membranes and adopts random coil conformation at the physiological pH. The peptide switches from random coil to α-helical conformation and inserts unidirectionally into membrane bilayers when pH drops below a critical transition value that has been routinely determined by the Trp fluorescence spectroscopy. Recent high-resolution studies using solid-state NMR spectroscopy revealed the presence of thermodynamically stable intermediate states of membrane-associated pHLIP around the fluorescence-based transition pH-value. However, the molecular structural features and their mechanistic roles of these in

SUBMITTER: Otieno SA 

PROVIDER: S-EPMC8595900 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature