Monomer Self-Assembly for Oral Protein Interaction Disruption
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Solution Overview
Problem
Current drug design and therapies fail to effectively modulate protein-protein interactions, particularly across extended areas or multiple domains of biomolecules, such as proteins, which is crucial for addressing conditions like cancer, as existing drugs are either too large for oral administration or lack the capability to disrupt protein-protein surface interactions effectively.
Innovation Solution
Development of monomers capable of forming biologically useful multimers in an aqueous media, specifically dimers or higher-order structures, comprising a ligand moiety, a linker element, and a connector element that can bind to multiple protein domains simultaneously, using boronic acid or oxaborole moieties to form stable complexes with proteins like tryptase.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies and other biological therapeutic agents are used to achieve sufficient specificity to distinguish among closely related protein surfaces, then binding specificity is improved, but molecular weight becomes too large for oral administration and uptake
Solution Approach 1:
The patent divides the therapeutic agent into small molecular weight components (monomers) that can be orally administered, which then self-assemble into multimeric structures that achieve the binding specificity previously only available from large antibodies. This segmentation resolves the contradiction by separating the administration form (small molecules) from the active form (multimeric complexes).
Solution Approach 2:
The patent creates composite multimeric structures composed of multiple small molecule monomers that self-assemble through non-covalent interactions. These composite structures combine the advantages of small molecules (oral bioavailability) with the advantages of large biologics (high binding specificity and avidity).
2Ease of operation
If orally active pharmaceuticals are used to achieve small molecular size for oral administration, then ease of administration is improved, but the molecules are too small to disrupt protein-protein surface interactions
Solution Approach 1:
The patent merges multiple small molecule pharmacophores into multimeric assemblies that function as a single therapeutic entity. This merging allows the retention of oral administrability while achieving the molecular footprint and binding capability needed to disrupt protein-protein interactions.
Solution Approach 2:
The patent constructs composite multimeric structures from small molecule components, creating assemblies with enhanced molecular weight and surface area that can effectively engage with protein-protein interaction interfaces while maintaining the oral bioavailability characteristics of small molecules.
3Adaptability or versatility
If large covalently linked compounds are assembled in organic solvents to link two pharmacophores, then the ability to interact with different protein domains is improved, but molecular weight becomes too large for oral administration and cellular permeation
Solution Approach 1:
The patent employs self-service principles where the monomers autonomously self-assemble into multimeric structures through non-covalent interactions in aqueous environments. This eliminates the need for complex covalent linking chemistry and organic solvents, enabling oral administration while maintaining the ability to interact with multiple protein domains.
Solution Approach 2:
The patent inverts the conventional approach by instead of covalently linking pharmacophores to create large molecules, it uses non-covalent self-assembly of small molecules to create functional multimers. This inversion resolves the contradiction by achieving multi-domain interaction capability through reversible associations rather than permanent covalent bonds.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These multimeric compounds can modulate multiple biomolecule domains simultaneously, offering enhanced binding affinity and therapeutic potential for diseases associated with protein-protein interactions, such as cancer and inflammatory conditions, by forming stable complexes that disrupt or regulate protein function.
Implementation Method 1
the second monomer has a boronic acid or oxaborole moiety capable of binding with the Z1 moiety of Formula I to form the multimer
Data Source
AI summary
Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.