US 11,919,972 B2
Peptide libraries with non-canonical amino acids
Anders Eliasen, Culver City, CA (US)
Assigned to REGENERON PHARMACEUTICALS, INC., Tarrytown, NY (US)
Filed by REGENERON PHARMACEUTICALS, INC., Tarrytown, NY (US)
Filed on Nov. 4, 2019, as Appl. No. 16/673,657.
Claims priority of provisional application 62/755,403, filed on Nov. 2, 2018.
Prior Publication US 2020/0140487 A1, May 7, 2020
Int. Cl. C07K 7/06 (2006.01); A61K 49/00 (2006.01); A61K 49/14 (2006.01); A61K 51/08 (2006.01); C12N 15/10 (2006.01); G01N 33/68 (2006.01)
CPC C07K 7/06 (2013.01) [A61K 49/0002 (2013.01); A61K 49/14 (2013.01); A61K 51/08 (2013.01); C12N 15/1072 (2013.01); G01N 33/68 (2013.01)] 28 Claims
 
1. A cyclic peptide having the following structure (I):

OG Complex Work Unit Chemistry
or a salt, tautomer, prodrug or stereoisomer thereof, wherein:
L1 and L2 are each individually optionally substituted linker moieties, each linker moiety optionally comprising a linkage to a solid support, a linkage to a reporter moiety, a linkage to a peptide ligand, a linkage to an azide or alkyne moiety, or combinations thereof;
G is a triazole;
M is absent or methionine;
R is H, -L3-A or —C(═O)-L3-A, where L3 is a linker moiety and A is an alkyne, azide, or a bond to a peptide ligand;
R1 is H or C1-C6 alkyl;
y1 and y2 are each individually 0 or 1; and
SEQ is an amino acid sequence comprising from 2 to 20 amino acids selected from the group consisting of: L-alanine, L-glycine, L-leucine, L-isoleucine, L-valine, L-phenylalanine, L-tryptophan, L-arginine, L-histidine, L-lysine, L-aspartic acid, L-glutamic acid, L-asparagine, L-glutamine, L-serine, L-threonine, L-tyrosine, L-proline, D-alanine, D-glycine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tryptophan, D-arginine, D-histidine, D-lysine, D-aspartic acid, D-glutamic acid, D-asparagine, D-glutamine, D-serine, D-threonine, D-tyrosine, D-proline, Cyclopropyl Alanine (CyA), Methyl Leucine (MeL), Methyl Valine (MeV), Allylglycine, Methyl Tryptophan (MT), Thiazolyl Alanine (Thz), 2-Naphthyl Alanine (Nap), O-Methyl Tyrosine (OMY), 4-Fluorophenyl Alanine (FP), 4-Cyano Phenylalanine (CN—F), 4-Phenyl Phenylalanine (PhF), 4-Bromo Phenylalanine (Br—F), 4-Pyridyl Alanine (PyrA), 4-Methyl Phenylalanine (Me-F), O-Phenyl Tyrosine (OPhY), β-Phenylalanine (BPhA), Dimethyl Lysine (DMK), 2-Methoxy Pyridylalanine (MeOPyr), Piperazinecarboxylic acid, N-Methyl d-valine (N-Me-v), N-Methyl d-alanine (N-Me-a), Aminocyclobutyl carboxylic acid (ACBC), Aminocyclohexyl carboxylic (ACHC), α-Methyl Alanine (AMA), Morpholinecarboxylic acid, Tetrazoyl Alanine (Ttz), β-Alanine (BAla), and Azetidine carboxylic acid, and
wherein at least one amino acid in SEQ is CyA, MeL, MeV, Allylglycine, MT, Thz, Nap, OMY, FP, CN—F, PhF, Br—F, PyrA, Me-F, OPhY, BPhA, DMK, MeOPyr, Piperazinecarboxylic acid, N-Me-v, N-Me-a, ACBC, ACHC, AMA, Morpholinecarboxylic acid, Ttz, BAla, or Azetidine carboxylic acid.