Bioactive peptide brush polymers via photoinduced reversible-deactivation radical polymerization

Patent metadata

Field	Value
Publication number	US-12516145-B2
Application number	US-202017764746-A
Country	US
Kind code	B2
Filing date	Sep 29, 2020
Priority date	Sep 30, 2019
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

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.

First claim

We claim:

1 . 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.

2 . The method of claim 1 , wherein the one or more photoinitiators comprise eosin Y disodium, pentamethyldiethylenetriamine, sodium phenyl-2,4,6-trimethylbenzoylphosphinate, lithium phenyl-2,4,6-trimethylbenzoylphosphinate, Zn(II) meso-Tetra(4-sulfonatophenyl) porphine, or a combination of these.

3 . The method of claim 1 , wherein the one or more chain transfer agents comprises a chain transfer agent characterized by formula FX13:

4 . The method of claim 1 , the method comprising metal-free photoinduced reversible-deactivation radical polymerization and/or photo-electron transfer reversible addition-fragmentation transfer polymerization.

5 . The method of claim 1 , wherein each peptide-containing monomer is independently characterized by formula FX1:
Z-(A-Pep) x   (FX1); wherein:
Z is a polymer backbone precursor group; A is a covalent anchor group; Pep is a peptide moiety; and x is an integer selected from the range of 1 to 2.

6 . The method of claim 5 , wherein each Pep comprises a sequence having at least 80% sequence homology with SEQ ID NO:1 (GPLGLAGGWGERDGS), SEQ ID NO:2 (GALTPRGADSGSG), SEQ ID NO:3 (KLAKLAKKLAKLAK), SEQ ID NO:4 (GSGKEFGADSGSG), SEQ ID NO:5 (GPLGLAGG), SEQ ID NO:6 (HVLVMSATKKKK), SEQ ID NO:7 (GGGCYFQNCPKG) (Terlipressin), SEQ ID NO:8 (DRVYIHPF) (Angiotensin 2), SEQ ID NO:9 (AQYQDKLAR) (DA1), SEQ ID NO:10 (GVi (allo) SQIRP) (ABT898), SEQ ID NO:11 (KVPRNQDWL) (gp100), SEQ ID NO:12 (GPLGLAGGWGER), or a combination of these.

7 . The method of claim 1 , wherein the peptide brush polymer is characterized by formula FX6A or FX6B:
Q 1 -[B 1 ] m -Q 2   (FX6A); or
Q 1 -[B 1 ] m —/—[B 2 ] n -Q 2   (FX6B); wherein:
each B 1 is independently a peptide-containing polymer block; each B 2 is independently a peptide-free polymer block; each of m and n is independently an integer greater than or equal to 1; the symbol “/” indicates that the units separated thereby are covalently linked randomly or in any order; and each of Q 1 and Q 2 is independently a polymer terminating group.

8 . The method of claim 7 , wherein each B 1 is characterized by the formula (FX7):

wherein:
each U 1 is independently a peptide-containing repeating unit;
each U 2 is independently a peptide-free repeating unit;
a is an integer selected from the range of 2 to 100;
b is 0 or an integer selected from the range of 2 to 100; and
the symbol “/” indicates that the units separated thereby are covalently linked randomly or in any order.

9 . The method of claim 8 , wherein each U 1 is independently characterized by the formula FX8A or FX8B and each U 2 , if present, is independently characterized by the formula FX9A or FX9B:

wherein:
each G is independently a polymer backbone group;
each A is independently a covalent anchor group;
each Pep is independently a peptide moiety; and
each M is independently an alkyl group, an alkenylene group, an arylene group, an alkoxy group, an acyl group, a carboxyl group, an aliphatic group, an amide group, an aryl group, an amine group, an ether group, a ketone group, an ester group, or combinations thereof.

10 . The method of claim 9 , wherein the peptide brush polymer is characterized by formula FX11A or FX11B:

11 . The method of claim 9 , wherein the peptide brush polymer is characterized by formula FX12:

Assignees

• Univ Northwestern

Inventors

• Gianneschi Nathan C
• Sun Hao

Classifications

• C08F2438/03

  Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX] · CPC title

• C08F220/56

  Acrylamide; Methacrylamide · CPC title

• C08F2/50

  with sensitising agents · CPC title

• C08F2/10

  Aqueous solvent · CPC title

• C08F2/06

  Organic solvent · CPC title