Biosynthetically generated pyrroline-carboxy-lysine and site specific protein modifications via chemical derivatization of pyrroline-carboxy-lysine and pyrrolysine residues

A compound having the structure of Formula (II):

• R1-(BB)n-R2 (II)
• wherein:
• R1 is H or an amino terminus modification group;
• R2 is OH or a carboxy terminus modification group;
• n is an integer from 1 to 5000;
• each BB is independently selected from an amino acid residue, a pyrrolysine analogue amino acid residue having the structure of Formula (D-1), and a pyrrolysine analogue amino acid residue having the structure of Formula (F 1):
• wherein:
• R5 is selected from H, —OH, —NO2, halo, C1-8alkyl, halo-substituted-C1-8alkyl, hydroxy-substituted-C1-8alkyl, aryl, heteroaryl, heterocycloalkly or cycloalkyl and -LX1;
• R6 is H or C1alkyl;
• A is a phenyl optionally substituted with 1 to 3 substituents independently selected from —OH, —NO2, halo, C1-8alkyl, halo-substituted-C1-8alkyl, hydroxy-substituted-C1-8alkyl, aryl, heteroaryl, heterocycloalkly, or cycloalkyl and -LX1;
• L is selected from a bond, C1-8alkylene, halo-substituted-C1-8alkylene, hydroxy-substituted-C1-8alkylene, C2-8alkenylene, halo-substituted-C2-8alkenylene, hydroxy-substituted-C2-8alkenylene,
• —O(CR11R12)k—, —S(CR11R12)k, —S(O)k(CR11R12)k—, —O(CR11R12)k—NR11C(O)—, —O(CR11R12)kC(O)NR11—, —C(O)—, —C(O)(CR11R12)k—, —C(S)—, —C(S)(CR11R12)k—, —C(O)NR11—, —NR11C(O)—, —NR11(CR11R12)k—, —CONR11(CR11R12)k—, —N(R11)CO(CR11R12)k—, —C(O)NR11(CR11R12)k—, —NR11C(O)CR11R12)k—, where each R11 and R12 are independently H, C1-8alkyl, halo-substituted-C1-8alkyl, or hydroxy-substituted-C1-8alkyl, and k is an integer from 1 to 12, and
• X1 is selected from a water-soluble polymer, a polyalkylene glycol, a poly(ethylene glycol), a derivative of poly(ethylene glycol), a sugar, a lipid, a cytotoxic compound, an affinity label, a peptide, a protein, an antibody or antibody fragment, a carbohydrate, a DNA, a RNA, phosphorothioate-modified DNA, a saccharide, a disaccharide, an oligosaccharide, a polysaccharide, a spin label, a fluorophore, a radioactive moiety a photocaged moiety, biotin, a biotin analogue, a TLR2 agonist, a TLR4 agonist, a TLR7 agonist, a TLR9 agonist, a TLR8 agonist, a T-cell epitope, a phospho-lipid, a LPS-like molecule, an immunogenic hapten, an immune response potentiator, a solid support, —CH2CH2—(OCH2CH2O)p—OX2, —O—(CH2CH2O)pCH2CH2—X2, and any combination thereof, wherein p is 1 to 10,000 and X2 is H, a C1-8alkyl, a protecting group or a terminal functional group, and
• wherein:
• at least one BB in the compound of Formula (II) is a pyrrolysine analogue amino acid residue having the structure of Formula (D-1).