Yuanjun Liang

Tunable self-assembled peptide amphiphile nanostructures.

Peptide amphiphiles are capable of self-assembly into a diverse array of nanostructures including ribbons, tubes, and vesicles. However, the ability to select the morphology of the resulting structure is not well developed. We examined the influence of systematic changes in the number and type of hydrophobic and hydrophilic amino acids on the self-assembly of amphiphilic peptides. Variations in the morphology of self-assembled peptides of the form X(6)K(n) (X = alanine, valine, or leucine; K = lysine; n = 1-5) are investigated using a combination of transmission electron microscopy and dynamic light scattering measurements. The secondary structures of the peptides are determined using circular dichroism. Self-assembly is controlled through a combination of interactions between the hydrophobic segments of the peptide molecules and repulsive forces between the charged segments. Increasing the hydrophobicity of the peptide by changing X to a more lipophilic amino acid or decreasing the number of hydrophilic amino acids transforms the self-assembled nanostructures from vesicles to tubes and ribbons. Changes in the hydrophobicity of the peptides are reflected in changes in the critical micelle concentration observed using pyrene probe fluorescence analysis. Self-assembled materials formed from cationic peptide amphiphiles of this type display promise as carriers for insoluble molecules or negatively charged nucleic acids in drug or gene delivery applications.

Design, synthesis, and activity evaluation of novel erythropoietin mimetic peptides

The approval of the erythropoietin (EPO) mimetic peptide drug peginesatide in 2012 was a breakthrough for the treatment of secondary anemia. However, due to severe allergic reactions, peginesatide was recalled a year later. In this study, 12 novel peptides were designed and synthesized by substituting specific amino acids of the monomeric peptide in peginesatide, with the aim of obtaining new EPO mimetic peptides with higher activities and lower side effects than the parent compound. Their cell proliferation activities were evaluated, and the structure-activity relationships were analyzed. Five compounds had equal cell proliferation activity to the control peptide. Among them, one compound showed a higher in vivo activity than the control peptide, with no obvious side effects.