US 8,557,781 B2Granted

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

AssigneeAmbrx, Inc.

InventorsZhenwei Miao, Junjie Liu, Thea Norman

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Abstract

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 aromatic amine 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 alkylated amine 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.

Claims12

Dependent claims

A compound or salt thereof selected from the group consisting of:

wherein each Ra is independently selected from the group consisting of H, halogen, alkyl, —NO2, —CN, substituted alkyl, —N(R′)2, —C(O)kR′, —C(O)N(R′)2, —OR′, and —S(O)kR′, where k is 1, 2, or 3;
M is H or —CH2R5;
or the M-N—C(R5) moiety forms a 4 to 7 membered ring structure;
R1 is H, an amino protecting group, or at least one amino acid without an amino protecting group;
R2 is OH, an ester protecting group, or at least one amino acid without an ester protecting group;
wherein at least one of R1 and R2 is at least one amino acid;
R5 is alkyl, substituted alkyl, polyalkylene oxide, substituted polyalkylene oxide, aryl, heteroaryl, -(alkylene)-(aryl), -(alkenylene)-(aryl);
or R5 is L-X, where, X is polyalkylene oxide or substituted polyalkylene oxide;
and L is a linker selected from the group consisting of alkylene, alkenylene, —O—, —O-(alkylene)-, -(alkylene)-O—, —C(O) —, —C(O)-(alkylene)-, -(alkylene)-C(O)—, —C(O)N(R′)—, —C(O)N(R′)-(alkylene)-, -(alkylene)-C(O)N(R′), —OC(O)N(R′)—, —OC(O)N(R′)-(alkylene)-, -(alkylene)-OC(O)N(R′)—, —N(R′)C(O)—, —NR′C(O)-(alkylene)-, -(alkylene)-NR′C(O)—, —S—, —S—(alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene)-, —C(S)—, —C(S)-(alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene)-, —N(R′)CO-(alkylene)-, —N(R′)C(O)O—, -(alkylene)-O—N═CR′—, -(alkylene)-C(O)NR′-(alkylene)-, -(alkylene)-S(O)k-(alkylene or substituted alkylene)-S—, -(alkylene)-S—S—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —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′)—;
and
each R′ is independently H, alkyl, or substituted alkyl.

8 more elements

A method of making a compound containing at least one non-natural amino acid selected from the group consisting of:

the method comprising:
reductively alkylating an aromatic amino moiety on at least one non-natural amino acid with at least one reactant comprising at least one aldehyde moiety;
wherein each Ra is independently selected from the group consisting of H, halogen, alkyl, —NO2, —CN, substituted alkyl, —N(R′)2, —C(O)kR′, —C(O)N(R′)2, —OR′, and —S(O)kR′, where k is 1, 2, or 3;
M is H or —CH2R5;
or the M-N—C(R5) moiety forms a 4 to 7 membered ring structure;
R1 is H, an amino protecting group, or at least one amino acid without an amino protecting group;
R2 is OH, an ester protecting group, or at least one amino acid;
R5 is alkyl, substituted alkyl, polyalkylene oxide, substituted polyalkylene oxide, aryl, heteroaryl, -(alkylene)-(aryl), or -(alkenylene)-(aryl);
or R5 is L-X, where, X is polyalkylene oxide or substituted polyalkylene oxide;
and L is a linker selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, —O—, —O-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)-O—, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)-C(O)—, —C(O)N(R′)—, —C(O)N(R′)-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)-C(O)N(R′), —OC(O)N(R′)—, —OC(O)N(R′)-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)-OC(O)N(R′)—, —N(R′)C(O)—, —NR′C(O)-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)-NR′C(O)—, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R′)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, -(alkylene or substituted alkylene)-O—N═CR′—, -(alkylene or substituted alkylene)-C(O)NR′-(alkylene or substituted alkylene)-, -(alkylene or substituted alkylene)-S(O)k-(alkylene or substituted alkylene)-S—, -(alkylene or substituted alkylene)-S—S—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —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′)—;
and
each R′ is independently H, alkyl, or substituted alkyl.

9 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/925,732Filed 26 Oct 2007 · continuation
Priority: 14 Dec 2005
Published: US 2008/0118464 A122 May 2008
Granted: 15 Oct 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
C07K 2/00
Peptides of undefined number of amino acids
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

Application60/743,041Us provisional application · filed 14 Dec 2005
Application60/743,040Us provisional application · filed 14 Dec 2005
PCT/US2006/047822Parent of this continuation · filed 13 Dec 2006
US 2008/0118464 A1Pre-grant publication · published 22 May 2008
US 8,557,781 B2This patent

From the US filing history. Foreign family members aren’t listed.