Proximity-inducing modalities: the past, present, and future.

Area of Science:

• Molecular Biology
• Biochemistry
• Drug Discovery

Background:

• Living organisms naturally utilize proximity to regulate biochemical processes.
• Bifunctional modalities are engineered molecules that induce proximity to redirect cellular functions.
• Early successes focused on inducing protein degradation via the ubiquitin-proteasome system.

Purpose of the Study:

• To review emerging bifunctional modalities beyond protein degradation.
• To highlight their potential in disease treatment and basic biological research.
• To explore novel applications in modulating cellular processes.

Main Methods:

• Literature review of recent advancements in bifunctional modality development.
• Analysis of modalities targeting protein phosphorylation, glycosylation, and acetylation.
• Examination of tools modulating gene expression and immune system components.

Main Results:

• Bifunctional modalities can now alter protein post-translational modifications.
• These molecules offer new ways to control gene expression.
• Immune system recruitment is a newly explored function of these modalities.

Conclusions:

• Bifunctional modalities represent a versatile class of molecular tools.
• Applications extend beyond degradation to diverse cellular regulation.
• These tools hold significant promise for therapeutic development and biological discovery.