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US 2026/0062449 A1Published application
Peptide compositions and methods of use
AssigneeONL Therapeutics, Inc.
InventorsAndrew J. KOCAB, David N. ZACKS, Alexander J. BRIDGES
Life of this patent
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Abstract
Provided herein are compositions including peptides, pharmaceutical preparations thereof, and methods of preventing photoreceptor death therewith and protecting of retinal cells, including, but not limited to, photoreceptors and retinal pigment epithelium, from Fas- or TRAIL-mediated apoptosis.
Claims58
An oligopeptide or peptidomimetic of Formula (Ia) or Formula (Ib):
- or pharmaceutically acceptable salt thereof, wherein:
- J1, J2, and J3 are each optional linker regions consisting of one to six amino acid residues;
- Z1, Z1′, Z2, and Z2′ are each independently selected from glycine (G), alanine (A), and serine (S);
- Z3, Z3′, Z4, and Z4′ are each an amino acid residue selected from histidine (H), tyrosine (Y), phenylalanine (F), and tryptophan (W);
- X1 and X1′ are each a tripeptide region consisting of three amino acid residues, wherein at least one amino acid residue is selected from histidine (H), lysine (K), arginine (R), alanine (A), cysteine (C), and methionine (M), and one amino acid residue is selected from leucine (L), isoleucine (I), methionine (M), and valine (V);
- X2 and X2′ are each independently selected from (i) and (ii):
- (i) when Z3 and Z4 are each tyrosine (Y), Z1 is glycine (G), and Z2 is alanine (A) or when Z3′ and Z4′ are each tyrosine (Y), Z1′ is glycine (G), and Z2′ is alanine (A);
- X2 and X2′ are each selected from leucine (L), isoleucine (I), alloisoleucine, methionine (M), serine (S), and threonine (T);
- or
- (ii) when at least one of Z3 and Z4 is not tyrosine (Y), Z1 is not glycine (G), or Z2 is not alanine (A), or when at least one of Z3′ and Z4′ is not tyrosine (Y) or Z1′ is not glycine (G), Z2′ is not alanine (A),
- X2 and X2′ are each selected from glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I), alloisoleucine, methionine (M), serine (S), and threonine (T);
- X3 and X3′ are each an amino acid residue selected from asparagine (N), glutamine (Q), serine (S), and threonine (T);
- R1 is selected at each occurrence from hydrogen, —C(O)C1-4 alkyl, and B—R3;
- R2 is selected at each occurrence from hydrogen and B—R3;
- wherein B is absent or an organic linker, and R3 is a label or a water-soluble oligomer;
- wherein the amino acid residues of X1, X2, X3, Z1, Z2, Z3 and Z4 are L-amino acid residues, and the amino acid residues of X1′, X2′, X3′, Z1′, Z2′, Z3′ and Z4′ are D-amino acid residues.
13 more elements
An oligopeptide or peptidomimetic of Formula (IIa) or Formula (IIb):
- or pharmaceutically acceptable salt thereof, wherein:
- J11, J12, and J13 are each optional linker regions consisting of one to six amino acid residues;
- Z11 and Z11′ are each an amino acid residue selected from:
- tyrosine (Y), phenylalanine (F), tryptophan (W), alanine (A), valine, (V), leucine (L), isoleucine (I), alloisoleucine, and methionine (M);
- Z12 and Z12′ are each an amino acid residue selected from:
- glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I), and alloisoleucine;
- Z13, Z14, Z13′, and Z14′ are each an amino acid residue selected from histidine (H), tyrosine (Y) phenylalanine (F), and tryptophan (W);
- X11 and X11′ are each a tripeptide region consisting of three amino acid residues, wherein at least one amino acid residue is selected from histidine (H), lysine (K), arginine (R), alanine (A), cysteine (C), and methionine (M), and one amino acid residue is selected from leucine (L), isoleucine (I), methionine (M), and valine (V);
- provided that at most one of the three amino acid residues of X11 and X11′ is histidine;
- X12 and X12′ are each an amino acid residue selected from glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I), and methionine (M);
- X13 and X13′ are each an amino acid residue selected from valine (V), leucine (L), isoleucine (I), alloisoleucine, methionine (M), phenylalanine (F), and tyrosine (Y);
- R11 is selected at each occurrence from hydrogen, —C(O)C1-4 alkyl, and B—R13;
- R12 is selected at each occurrence from hydrogen and B—R13;
- wherein B is absent or an organic linker, and R13 is a label or a water-soluble oligomer;
- wherein the amino acids of X11, X12, Z11, Z12, Z13, and Z14 are L-amino acids, and the amino acids of X11′, ×12′, Z11′, Z12′, Z13′, and Z14′ are D-amino acids.
12 more elements
An oligopeptide or peptidomimetic of Formula (IIIa) or Formula (IIIb):
- or pharmaceutically acceptable salt thereof, wherein
- J21, J22, J23 are each optional linker regions consisting of one to six amino acid residues;
- Z21, Z21′, Z22 and Z22′ are each independently selected from:
- glycine (G), alanine (A), and serine (S);
- Z23, Z24, Z23′, and Z24′ are each an amino acid residue selected from histidine (H), tyrosine (Y), phenylalanine (F), and tryptophan (W);
- X21 and X21′ are each a tripeptide region comprising one to six amino acid residues, each of which is independently selected from:
- histidine (H), lysine (K), arginine (R), alanine (A), cysteine (C), and methionine (M), and one amino acid residue is selected from leucine (L), isoleucine (I), methionine (M), and valine (V);
- X22 and X22′ are each independently selected from glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I), alloisoleucine, methionine (M), serine (S), and threonine (T);
- X23 and X23′ are each an amino acid residue selected from asparagine (N), glutamine (Q), serine (S), and threonine (T);
- R21 is selected at each occurrence from hydrogen, —C(O)C1-4 alkyl, and B—R23;
- R22 is selected at each occurrence from hydrogen and B—R23, wherein at least one occurrence of R21 or R22 is selected from —C(O)C1-4 alkyl and B—R23;
- wherein B is absent or an organic linker, and R23 is a label or a water-soluble oligomer;
- wherein the amino acid residues of X21, X22, X23, Z21, Z22, Z23 and Z24 are L-amino acid residues, and the amino acid residues of X21′, X22′, X23′, Z21′, Z22′, Z23′ and Z24′ are D-amino acid residues.
10 more elements
Dependencies are inferred from the claim text.