Macrocycles as protein-protein interaction inhibitors

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Chemical Biology

Background:

• Intracellular protein-protein interactions (PPIs) are challenging drug targets for traditional modalities.
• Macrocyclic compounds, particularly cyclic peptides, offer a novel therapeutic approach.
• Recent advancements facilitate the synthesis and screening of macrocycle libraries.

Purpose of the Study:

• To review technologies for synthesizing and screening macrocyclic compound libraries.
• To discuss strategies for enhancing the membrane permeability of cyclic peptides.
• To highlight applications in discovering macrocyclic inhibitors of protein-protein interactions.

Main Methods:

• Development of complementary technologies for macrocycle synthesis.
• Screening methodologies for identifying macrocyclic binders to therapeutic targets.
• Exploration of approaches to improve cyclic peptide membrane permeability.

Main Results:

• Macrocyclic compounds show potential as inhibitors of intracellular PPIs.
• Diverse technologies enable library synthesis and target screening.
• Strategies exist to enhance membrane permeability for improved drug delivery.

Conclusions:

• Macrocycles represent a viable new class of drugs targeting PPIs.
• Technological advancements are driving macrocycle-based drug discovery.
• Further research into membrane permeability is crucial for clinical translation.