Linker Chemistry Determines Secondary Structure of p5314-29 in Peptide Amphiphile Micelles

Biofunctional micelles formed via self-assembly of synthetic peptide-lipid conjugates arc a class of promising biomaterials with applications in drug delivery and tissue engineering. The micelle building block, termed peptide amphiphile, consists of a lipid-like chain covalently linked through a spacer to a peptide headgroup. Self-assembly results in formation of a hydrophobic core surrounded by a dense shell with multiple, functional peptides. We report here on the effect that different linkers between a palmitic tail and a bioactive peptide (p53(14-29)) have on headgroup secondary structure. Peptide p53(14-29) may act as an inhibitor of the interaction between tumor suppressor p53 and human double minute-2 (hDM2) proteins by binding hDM2 in a partially helical form, leading to the release of p53 and the induction of apoptosis in Certain Minors. Circular dichroism and fluorescence Spectroscopy data revealed that the extent and type of secondary Structure of p53(14-29) are controlled through size and hydrogen bond potential of the linker. In addition, the structure of the self-assembled micelles was influenced through linker-dependent altered headgroup interactions. This Study provides insight into the mechanisms through Which headgroup structuring occurs oil peptide amphiphile micelles, with implications oil the bioactivity, stability, and morphology of the self-assembled entities.