Methods of forming radiopaque peptides and medical hydrogels formed therefrom

A hydrogel comprising a crosslinked reaction product of a radiopaque peptide compound and a reactive polymer that comprises moieties that react with the radiopaque peptide compound to form covalent linkages, wherein the iodinated peptide compound is provided by a method that comprises:

• (a) forming a multifunctional precursor compound comprising (i) an amine-protected peptide residue that comprises two or more amino acid residues with primary-amine-containing side groups and (ii) a multifunctional moiety linked to the amine-protected peptide residue through an amide group or an ester group, the multifunctional moiety further comprising n primary amine groups, n hydroxyl groups, or n carboxyl groups, wherein n is an integer of 2 or more;
• (b) reacting the multifunctional precursor compound in an amide coupling reaction or an ester coupling reaction with an iodinated compound selected from an amine-functional iodinated compound that comprises an iodinated moiety, a carboxyl-functional iodinated compound that comprises an iodinated moiety, and a hydroxy-functional iodinated compound that comprises an iodinated moiety, to form an iodinated, amine-protected peptide compound comprising n iodinated moieties that are covalently attached to the amine-protected peptide residue through a residue of the multifunctional moiety;
• and (c) deprotecting the iodinated, amine-protected peptide compound to form the iodinated peptide compound.

A system that comprises a first composition that comprises a radiopaque peptide compound and a second composition that comprises a reactive polymer that comprises moieties that react with the radiopaque peptide compound, wherein the system is configured to deliver the reactive polymer and the radiopaque peptide compound under conditions such that covalent crosslinks are formed between the reactive polymer and the radiopaque peptide compound, and wherein the iodinated peptide compound is provided by a method that comprises:

• (a) forming a multifunctional precursor compound comprising (i) an amine-protected peptide residue that comprises two or more amino acid residues with primary-amine-containing side groups and (ii) a multifunctional moiety linked to the amine-protected peptide residue through an amide group or an ester group, the multifunctional moiety further comprising n primary amine groups, n hydroxyl groups, or n carboxyl groups, wherein n is an integer of 2 or more;
• (b) reacting the multifunctional precursor compound in an amide coupling reaction or an ester coupling reaction with an iodinated compound selected from an amine-functional iodinated compound that comprises an iodinated moiety, a carboxyl-functional iodinated compound that comprises an iodinated moiety, and a hydroxy-functional iodinated compound that comprises an iodinated moiety, to form an iodinated, amine-protected peptide compound comprising n iodinated moieties that are covalently attached to the amine-protected peptide residue through a residue of the multifunctional moiety;
• and (c) deprotecting the iodinated, amine-protected peptide compound to form the iodinated peptide compound.