Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides

摘要

Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

主权项

1. A method for derivatizing an antibody or fragment thereof comprising at least one amino acid of Formula (I), the method comprising contacting the antibody or fragment with a reagent of Formula (XIX), wherein Formula (I) corresponds to: wherein: A is phenylene; B is a bond; J is R is alkyl; each R′ is independently H, alkyl, or substituted alkyl; R1 is H, an amino protecting group, or at least one amino acid; R2 is OH, an ester protecting group, or at least one amino acid; and R3 and R4 are H;wherein Formula (XIX) corresponds to: wherein:
X is a drug or a detectable label, wherein the detectable label is selected from a fluorescent, phosphorescent, chemiluminescent, chelating, intercalating, radioactive, and chromophoric moiety, and combinations thereof, or a polyalkylene glycol;L is optional, and when present is a linker selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, —O—, —O-(alkylene or substituted alkylene)-, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —N(R′)—, —NR′-(alkylene or substituted alkylene)-, —C(O)N(R′)—, —CON(R′)-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)NR′C(O)O-(alkylene or substituted alkylene)-, —O—CON(R′)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, N(R′)C(O)O-(alkylene or substituted alkylene)-, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)N(R′)-(alkylene or substituted alkylene)-, —N(R′)C(S)N(R′)—, —N(R′)S(O)kN(R′)—, —N(R′)—N═, —C(R′)═N—, —C(R′)═N—N(R)—, —C(R′)═N—N═, —C(R′)2—N═N—, and —C(R′)2—N(R′)—N(R′)—, where each R′ is independently H, alkyl, or substituted alkyl; L1 is optional, and when present, is —C(R′)p—NR′—C(O)O-(alkylene or substituted alkylene)- where p is 0, 1, or 2; W is —ON(R1)2, where each R1 is independently H or an amino protecting group; and n is 1.