α-Helix mimetics: outwards and upwards

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Drug Design

Background:

• Alpha-helices are vital secondary structures in protein-protein interactions (PPIs).
• Targeting PPIs with small molecule helix mimetics is a promising therapeutic strategy.
• First-generation helix mimetics had limited residue presentation on a single surface.

Purpose of the Study:

• To address the limitations of existing helix mimetics.
• To design and synthesize novel scaffolds for complex PPIs.
• To develop multi-sided and extended helix mimetics.

Main Methods:

• Rational design of small molecule scaffolds.
• Chemical synthesis of novel helix mimetics.
• Structural analysis of protein-protein interfaces.

Main Results:

• Identification of complex binding modes in therapeutically relevant PPIs.
• Development of new generations of helix mimetics.
• Focus on multi-sided and extended recognition surfaces.

Conclusions:

• Novel helix mimetics are needed to address complex PPIs.
• Advanced scaffolds are under development for challenging therapeutic targets.
• Multi-sided and extended designs offer improved PPI mediation potential.