molekulides

Molekulides are a class of synthetic organic compounds characterized by their unique molecular architecture, combining elements of both molecular and supramolecular chemistry. The term "molekulide" was coined to describe molecules that exhibit properties intermediate between traditional small-molecule drugs and larger biomacromolecules like proteins or nucleic acids. These compounds typically range in size between 500 and 2,000 Daltons, bridging the gap between low-molecular-weight drugs and biologics.

The defining feature of molekulides is their ability to adopt well-defined, often complex three-dimensional conformations, often stabilized by intramolecular interactions such as hydrogen bonding, hydrophobic packing, or metal coordination. This structural rigidity allows them to mimic the binding interfaces of larger biomolecules while retaining the advantages of small-molecule drug design, such as oral bioavailability and ease of synthesis. Molekulides are often designed to target protein-protein interactions (PPIs), which are historically challenging for traditional small-molecule drugs due to their large, flat, and often polar interfaces.

Research into molekulides has gained traction in recent years as a strategy to address the limitations of conventional drug discovery. By leveraging computational design tools, scientists can engineer molekulides to bind specifically to disease-relevant PPIs, potentially offering therapeutic benefits for conditions like cancer, neurodegenerative diseases, and infectious disorders. Early examples of molekulide-like molecules include certain macrocyclic compounds and peptide-like structures that exploit conformational constraints to enhance binding affinity and selectivity.

The development of molekulides represents an evolving field at the intersection of chemistry, structural biology, and drug discovery. While still in its infancy, this approach holds promise for expanding the chemical space available for therapeutic intervention, particularly in targeting undruggable protein interfaces. Ongoing research focuses on refining synthesis methods, improving computational prediction tools, and validating the efficacy of molekulides in preclinical and clinical settings.