Bioactive peptide brush polymers via photoinduced reversible-deactivation radical polymerization
Inventors
Gianneschi, Nathan C. • Sun, Hao
Assignees
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Publication Number
US-12516145-B2
Publication Date
2026-01-06
Expiration Date
Abstract
Aspects of the invention include a method for synthesizing a peptide brush polymer, the method comprising: exposing a mixture comprising peptide-containing monomers, one or more photoinitiators, and one or more chain transfer agents to a light sufficient to induce photopolymerization, and photopolymerizing the peptide-containing monomers in the mixture; wherein: the resulting peptide brush polymer comprises at least one peptide-containing polymer block; the at least one peptide-containing polymer block is characterized by a degree of polymerization of at least 10 and a peptide graft density of 50% to 100%; and at least one peptide moiety of the at least one peptide-containing polymer block has 5 or more amino acid groups.
Core Innovation
The invention relates to a method for synthesizing a peptide brush polymer by exposing a mixture comprising peptide-containing monomers, one or more photoinitiators, and one or more chain transfer agents to light sufficient to induce photopolymerization, and photopolymerizing the peptide-containing monomers in the mixture. The resulting peptide brush polymer comprises at least one peptide-containing polymer block having a degree of polymerization of at least 10 and a peptide graft density of 50% to 100%.
At least one peptide moiety of the peptide-containing polymer block has 5 or more amino acid groups. The method further defines peptide-containing monomers by peptide moieties having 80% or more sequence homology to one or more SEQ ID NO sequences, including sequences corresponding to Terlipressin, Angiotensin 2, DA1, ABT898, and gp100.
The peptide brush polymer architecture includes terminating groups Q1 and Q2, repeating units U1, peptide-containing repeating units, and a repeating block structure with random covalent linking. The approach supports photo-RDRP and/or photo-RAFT, photo-PISA chain extension of a peptide-containing RAFT macroCTA, and peptide brush blocks in aqueous solution able to form micelles or nanoparticles.
Claims Coverage
One independent claim set is provided. The independent claims center on a method for synthesizing peptide brush polymers and specify 4 main inventive features, with additional dependent refinements concerning peptide sequence homology and polymer architecture.
Photopolymerizing peptide-containing monomers in a photoinitiator and chain-transfer-agent mixture
Exposing a mixture comprising peptide-containing monomers, one or more photoinitiators, and one or more chain transfer agents to light sufficient to induce photopolymerization, and photopolymerizing the peptide-containing monomers in the mixture.
Peptide brush polymer with peptide-containing polymer block
The resulting peptide brush polymer comprises at least one peptide-containing polymer block.
Block degree of polymerization and peptide graft density
The at least one peptide-containing polymer block is characterized by a degree of polymerization of at least 10 and a peptide graft density of 50% to 100%.
Peptide moiety length
At least one peptide moiety of the at least one peptide-containing polymer block has 5 or more amino acid groups.
The claim coverage is centered on producing a peptide brush polymer via light-induced photopolymerization from peptide-containing monomers, with at least one peptide-containing polymer block meeting the stated degree of polymerization and peptide graft density constraints and containing peptide moieties having at least five amino acid groups.
Stated Advantages
Enzyme-responsive/pro-apoptotic peptide activity as described for enzyme-responsive and pro-apoptotic peptide sequences.
Improved cellular uptake and controllable cytotoxicity as stated in the document.
Formation of micelles/nanoparticles with high water solubility as stated in the document.
Enhanced proteolytic stability of KLA peptide on nanoparticle surfaces versus free peptide and KLA brush polymer.
Dose-dependent cytotoxicity in HeLa cells with effects related to graft density.
Mitochondria depolarization in JC-1 assays with CCCP as a positive control.
Maintaining a narrow molecular weight distribution during photo-PISA chain extension.
Quantitative monomer conversion.
Documented Applications
Potential therapeutic aqueous formulations and enzyme-triggered enzymatic digestion are described in the document.
Enzyme-triggered cleavage/enzymatic digestion for enzyme-responsive peptides is described as an application context.
Peptide brush polymer nanoparticle therapeutics, including KLA peptide display on nanoparticle surfaces and evaluation of proteolytic stability, cytotoxicity in HeLa cells, cellular uptake, and mitochondria depolarization.
Formation of micelles or nanoparticles in aqueous solution.
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