I. Selection, synthesis, and mechanisms studies of cell-penetrating peptides: New drug delivery systems. II. Biological lessons for the preparation of Abeta(1-42) and cyclic peptide probe for the detection of botulinum neurotoxin A

Major obstacles in the development of new therapeutic anticancer drugs are the low bioavailability of hydrophilic substances and nonspecific toxicity towards healthy tissues. As such cell penetrating peptides (CPPs) have emerged as attractive drug delivery vehicles for a variety of different types of cargo. The ability to deliver a peptide to any cell type, let alone specifically targeting a tumor cell is a significant challenge because of the bioavailability restriction imposed by the cell membrane. The discovery of CPPs has opened up a plethora of possibilities in drug delivery, and various cargos have been exploited using CPPs.;This thesis begins with a brief history of cell-penetrating peptides in chapter 1 from the initial discovery of Tat peptide to the current uptake mechanism issues. Chapter 2 details the selection and characterization of two distinct cell-penetrating peptides that show unique cell internalization mechanisms against a variety of cancer cells using a library of phage displayed peptides. Chapter 3 details synthesis of the amyloid-beta protein (Abeta) by biological tuning. Chapter 4 completes this thesis with a development of inexpensive peptide-polymer-based capture ELISA system for rapid, sensitive and highly specific BoNT detection.