Triazole macrocycle systems
AssigneeAileron Therapeutics, Inc.
InventorHuw M. Nash
Life of this patent
Estimating the term…
Abstract
Provided herein are novel alkynyl and azide containing amino acids; kits containing these amino acids; peptides containing these amino acids; peptide macrocycles whose secondary structures are stabilized with linkers containing triazoles synthesized by reacting the side chains of the alkynyl and azide containing amino acids; and methods of making and using the alkynyl and azide containing amino acids, kits, peptides, triazole containing linkers, and peptide macrocycles.
Claims21
A compound of Formula IIa or IIb:
- wherein
- R1 and R2 are independently alkyl, which is unsubstituted or substituted with halo-;
- each Q and T is independently —CH2—;
- R7 and R8 are independently —H;
- R10 and R11 are independently —H;
- R12 is —H or alkyl;
- g and h are each independently-integers and g+h is 3, 4, 5, or 6;
- and
- the compound is enantiomerically enriched.
A kit comprising
- (a) at least one compound selected from the group consisting of compounds of Formulas IIa and IIb:
- wherein
- R1 is alkyl unsubstituted or substituted with halo-;
- R2 is alkyl unsubstituted or substituted with halo-;
- each Q and T is independently —CH2—;
- R7 and R8 are independently —H;
- R10 and R11 are independently —H;
- R12 is —H or alkyl;
- and
- g and h are each independently-integers and g+h is 3, 4, 5, or 6;
- the compound is enantiomerically enriched;
- and
- b) a macrocyclization reagent.
A compound selected from the group consisting of (S)-2-amino-2-methyl-5-hexynoic acid, (R)-2-amino-2-methyl-5-hexynoic acid, (S)-2-amino-2-methyl-6-heptynoic acid, (R)-2-amino-2-methyl-6-heptynoic acid, (S)-2-amino-2-methyl-7-octynoic acid, (R)-2-amino-2-methyl-7-octynoic acid, (S)-2-amino-2-methyl-8-nonynoic acid, (R)-2-amino-2-methyl-8-nonynoic acid, ε-azido-alpha-methyl-L-lysine, ε-azido-alpha-methyl-D-lysine, δ-azido-alpha-methyl-L-ornithine, and δ-azido-alpha-methyl-D-ornithine.
A compound selected from the group consisting of N-alpha-Fmoc-(S)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-epsilon-azido-alpha-methyl-L-lysine, N-alpha-Fmoc-epsilon-azido-alpha-methyl-D-lysine, N-alpha-Fmoc-delta-azido-alpha-methyl-L-ornithine, and N-alpha-Fmoc-delta-azido-alpha-methyl-D-ornithine.
A kit comprising:
- a) a compound selected from the group consisting of (S)-2-amino-5-hexynoic acid, (R)-2-amino-5-hexynoic acid, (S)-2-amino-6-heptynoic acid, (R)-2-amino-6-heptynoic acid, (S)-2-amino-7-octynoic acid, (R)-2-amino-7-octynoic acid, (S)-2-amino-8-nonynoic acid, (R)-2-amino-8-nonynoic acid, (S)-2-amino-2-methyl-4-pentynoic acid, (R)-2-amino-2-methyl-4-pentynoic acid, (S)-2-amino-2-methyl-5-hexynoic acid, (R)-2-amino-2-methyl-5-hexynoic acid, (S)-2-amino-2-methyl-6-heptynoic acid, (R)-2-amino-2-methyl-6-heptynoic acid, (S)-2-amino-2-methyl-7-octynoic acid, (R)-2-amino-2-methyl-7-octynoic acid, (S)-2-amino-2-methyl-8-nonynoic acid, (R)-2-amino-2-methyl-8-nonynoic acid, ε-azido-L-lysine, ε-azido-D-lysine, ε-azido-alpha-methyl-L-lysine, ε-azido-alpha-methyl-D-lysine, δ-azido-L-ornithine, δ-azido-D-ornithine, δ-azido-alpha-methyl-L-ornithine, and δ-azido-alpha-methyl-D-ornithine;
- and
- b) a macrocyclization reagent.
A kit comprising:
- a) a compound selected from the group consisting of N-alpha-Fmoc-(S)-2-amino-5-hexynoic acid, N-alpha-Fmoc-(R)-2-amino-5-hexynoic acid, N-alpha-Fmoc-(S)-2-amino-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-7-octynoic acid, N-alpha-Fmoc-(R)-2-amino-7-octynoic acid, N-alpha-Fmoc-(S)-2-amino-8-nonynoic acid, N-alpha-Fmoc-(R)-2-amino-8-nonynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-epsilon-azido-alpha-methyl-L-lysine, N-alpha-Fmoc-epsilon-azido-alpha-methyl-D-lysine, N-alpha-Fmoc-delta-azido-alpha-methyl-L-ornithine, N-alpha-Fmoc-delta-azido-alpha-methyl-D-ornithine, N-alpha-Fmoc-epsilon-azido-L-lysine, and N-alpha-Fmoc-epsilon-azido-D-lysine;
- and
- b) a macrocyclization reagent.
A compound selected from the group consisting of N-alpha-Fmoc-(S)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-7-octynoic acid, and N-alpha-Fmoc-(R)-2-amino-2-methyl-7-octynoic acid.
A compound selected from the group consisting of N-alpha-Fmoc-epsilon-azido-alpha-methyl-L-lysine, N-alpha-Fmoc-epsilon-azido-alpha-methyl-D-lysine, N-alpha-Fmoc-delta-azido-alpha-methyl-L-ornithine, and N-alpha-Fmoc-delta-azido-alpha-methyl-D-ornithine.
Dependencies are inferred from the claim text.