Modulation of The Condensate Scaffold for Drug Discovery

CD BioSciences offers a variety of condensate-based drug discovery strategies to achieve repair condensatopathy, disrupt the normal function of condensates associated with disease, and prevent targets from acting by disabling them in their natural condensates or by separating them from their natural condensates. Here, we help you with drug development by modulating the condensate scaffold.

Introduction of The Biomolecular Condensates Scaffold

Biomolecular condensates are membrane-free cellular compartments where groups of biomolecules, including proteins, RNA, or other molecules (including metabolites), assemble on length scales from nanometers to micrometers through extensive networks of interactions. The molecular composition of condensates is tightly controlled, with some components being constitutive and others only temporarily recruited under certain conditions. The "scaffold-client" model is used to explain this phenomenon. Scaffolds are multivalent molecules (usually proteins) that are associated with the stabilization of biomolecular cohesions and are essential for assembly. Clients, on the other hand, are transiently associated with condensate and may be recruited by the scaffold. Scaffolds are often considered to be the drivers of phase separation. Modulating condensate scaffolds can have a dramatic impact on condensate stability, such as persistence, C_sat, material properties, and/or composition.

Fig. 1. Compositional control of condensates formed from scaffolds with modular domains. (Ditlev J A, et al, 2018)

Our Solutions

CD BioSciences is actively exploring the disruption of the composition or stability of biomolecular condensates by altering weak network interactions. We offer professional drug discovery solutions by modulating condensate scaffolds. We aim to alter the assignment of biomolecules to specific condensates by modulating target-preferred interactions within or outside the condensate to allow for changes in condensate concentration thresholds, or by preferentially stabilizing conformational states to allow for increases or decreases in condensate thresholds.

Our modalities for modulating the condensate scaffold include:

• Adjusting the Chemical Valence
  Our team of experts can replace multivalent interactions with monovalent terminal interactions, thereby destabilizing network-stabilizing interactions in the coalescence. Our solutions are designed to do this by altering the chemical valence of self-assembled biomolecules, with decreases and increases in valency leading to condensate solubilization and induction, respectively.
• Blocking or Stabilizing Protein-Protein and Nucleic Acid Interactions
  Another of our strategies involves directly blocking or stabilizing the protein-protein, protein-nucleic acid, or nucleic acid-nucleic acid interactions that contribute to the condensate scaffold. CD BioSciences is at the forefront of developing compounds that target these interactions.

In addition to disrupting scaffold interactions, our solutions can stabilize non-productive conformations to prevent scaffolds from contacting, and capture the importance of abnormal proteins and excess proteins in inactive condensates. Our strategy demonstrates how modulating condensed scaffolds can affect the activity and localization of specific proteins, thus providing potential therapeutic pathways.

By tuning chemical valences, blocking interactions, and developing compounds with condensate-modulating activity, CD BioSciences aims to advance our understanding of condensate biology and harness its potential to treat a variety of diseases. Modulation of condensate scaffolds opens new avenues for precision medicine and targeted drug discovery, offering the promise of improved therapeutic interventions in the future. If you are interested in our solutions, please contact us now to seize new drug development opportunities.