Metal Ion Triggered Assembly of Peptide-Drug Conjugates | AIChE

Metal Ion Triggered Assembly of Peptide-Drug Conjugates

Authors 

Wang, H. - Presenter, The Johns Hopkins University
Su, H., Johns Hopkins University
Cui, H., Johns Hopkins University
Metal ions play a crucial role in determining protein structures as well as regulating important biological processes. Through coordination, metal ions can induce changes in biomolecule conformation so as to alter their assembly outcomes. In this work, we present our rational design of iron chelator bearing peptide-drug conjugates(PDCs) that could exhibit morphological transition in the presence/absence of Fe(III) ions. A series of PDCs with nitrilotriacetic acid or 2,3-dihydroxybenzoic acid as iron chelator were synthesized. Transmission electron microscopy revealed tubular nanostructures with diameters of ~7 nm before coordination with Fe3+. The binding of Fe3+ to the chelator in PDCs resulted in the formation of multiwalled nanotubes with outer diameters of ~120 nm and wall thickness up to 40 nm. The conformational transition is evidenced in the circular dichroism spectra at different Fe3+ concentrations, supporting a 1:2 ratio of metal to peptide monomer. Degradation studies revealed a difference in release kinetics of the free drug from chelated and non-chelated PDCs. We believe these results provide important insight into the rational design of iron-responsive drug delivery systems.