Design, Synthesis, and characterization of peptides from Gp36 FIV glycoprotein

Glycoproteins gp36 in FIV and gp41 in Human Immunodeficiency Virus (HIV) promote the fusion of virus envelope with the host cell membranes. They have a similar framework that includes the fusion peptide (FP), N-terminal heptad repeat (NHR), C-terminal heptad repeat (CHR), and membrane-proximal extracellular region (MPER). MPER is a hydrophobic, Trprich region characterized by a significant bio-membrane affinity. Virus entry is effective once NHR and CHR fold back to form a low-energy, stable six-helical bundle (6HB). MPER plays a significant role during this process by correctly driving the virus membrane to assemble with the host cell membrane. FIV and HIV entry can be efficiently inhibited by peptides mimicking conserved functional elements of Gp41 or Gp36. A prominent example of such peptides, termed fusion inhibitors, is the peptide T-20 (enfuvirtide, Fuzeon), which is used as salvage therapy for HIV/AIDS. We previously identified C8, a peptide belonging to the Gp36 MPER, that exhibited significant anti-FIV activity in vitro and in vivo. Extensive biophysical investigation indicated an unusual ability of C8 in interacting with phospholipid membrane and evidenced that the adsorption of C8 on the membrane causes membrane remodeling, with the formation of membrane "nipples" and tubes to create a tight network of membrane connections. Starting from these data, part of my Ph.D. research activity explored the possibility that the activity of C8 at the membrane level can be valuably used to promote cell differentiation and tissue regeneration. Therefore I produced C8 functionalized polycaprolactone (PCL) scaffolds and evaluated the ability of these devices to affect SH-SY5Y neuronal cells. Our data show that PCL can be efficiently functionalized with C8, and these scaffolds are efficient in promoting cell proliferation with modification of their shapes. In particular, PCL C8 functionalization induces better cell adhesion and spreading on the fiber surface, evidencing the ability to improve interaction with the material. [edited by Author]