Jumping Hurdles: Peptides Able To Overcome Biological Barriers

Area of Science:

• Peptide chemistry and drug delivery
• Biophysical chemistry
• Molecular biology

Background:

• Biological barriers like the cell membrane and blood-brain barrier (BBB) restrict hydrophilic compound passage.
• Cell-penetrating peptides (CPPs) and BBB shuttles offer novel strategies to overcome these barriers.
• Proline-rich peptides and their unique structural properties are key to developing new CPPs and BBB shuttles.

Purpose of the Study:

• To describe the development of proline-rich peptides, including CPPs and BBB shuttles.
• To analyze the structure and internalization mechanisms of these peptides.
• To highlight the potential of CPPs and BBB shuttles for therapeutic compound delivery.

Main Methods:

• Development of proline-rich peptides: proline-rich dendrimers, sweet arrow peptide (SAP), and γ-peptide foldamers.
• Investigation of BBB shuttles utilizing passive (e.g., diketoperazines) and active (e.g., SGV, THRre) transport mechanisms.
• Utilized peptide libraries (chemical and phage display) and hit-to-lead optimization.

Main Results:

• Successfully developed proline-rich CPPs with enhanced internalization properties.
• Designed BBB shuttles capable of crossing the BBB via both passive and active transport.
• Demonstrated the potential of these peptides for delivering therapeutic agents.

Conclusions:

• Proline-rich peptides offer versatile platforms for overcoming biological barriers.
• CPPs and BBB shuttles significantly enhance the delivery of therapeutic compounds.
• Further research into peptide design and transport mechanisms holds promise for advanced drug delivery systems.