US2014371079A1PendingUtilityA1
Cancer-targeting peptides and uses thereof in cancer treatment and diagnonsis
Est. expiryOct 25, 2030(~4.3 yrs left)· nominal 20-yr term from priority
A61K 31/337C07K 5/1024C07K 7/08A61K 51/1234A61K 38/10A61K 31/475A61K 47/6911A61K 9/127A61K 31/704A61K 45/06G01N 2500/04A61K 31/496A61K 49/0056G01N 2333/47A61K 49/0043A61P 35/00A61K 9/1271G06F 19/16G16B 15/00G16B 15/30
60
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Claims
Abstract
Cancer-targeting peptides having a PX 1 LX 2 motif, in which X 1 is His or an amino acid residue with a hydrophobic side chain and X 2 is Pro, Phe, or Trp. Also disclosed herein are conjugates containing the cancer-targeting peptides and uses thereof in cancer treatment and diagnosis.
Claims
exact text as granted — not AI-modified1 - 27 . (canceled)
28 . A method for structure-based optimization of a cancer-targeting peptide ligand, the method comprising:
(a) providing a cancer cell-surface protein; (b) calculating the Connolly surface of the cancer cell-surface protein; (c) identifying a peptide-binding site on the protein surface; (d) estimating distance-dependent potential of paired atoms involved in polar interactions comprising hydrogen bonding, ionic interactions and metal-ion coordination, the estimation comprising consideration of an intermolecular surface distance; (e) estimating distance-dependent potential of paired atoms involved in non-polar interactions, the estimation comprising application of Connolly surface of protein in calculation of the intermolecular surface distance; and (f) selecting a peptide ligand optimized for binding to the binding site of the cancer cell-surface protein from a peptide database based on the information obtained from steps (d) and/or (e).
29 . The method of claim 28 , wherein the Connolly surface of the cancer cell-surface protein is determined by the binding pocket analysis program PscanMS.
30 . The method of claim 28 , wherein the peptide database is combinatorially constructed.
31 . The method of claim 28 , wherein the cancer cell-surface protein is human glucose-regulated protein 78 (GRP-78).
32 . The method of claim 28 , wherein the intermolecular surface distance is determined based on the binding energy (ΔE) between protein (p) and ligand (l), which is calculated according to the following equation:
Δ
E
p
,
l
=
Δ
E
polar
(
δ
,
θ
,
φ
)
+
Δ
E
non
-
polar
(
v
,
A
)
,
(
φ
<
100
°
)
=
F
hbond
×
∑
h
(
cos
(
180
°
-
θ
h
)
×
W
hbond
(
δ
h
)
)
+
F
ion
×
∑
i
W
ion
(
δ
i
)
+
F
metal
×
∑
m
W
metal
(
δ
m
)
+
F
vdw
×
∑
v
(
A
v
×
W
vdw
(
v
v
)
)
wherein, h is the pair of H-bond; i is the pair of ionic interaction; m is the pair of metal-ion coordination and v is the ligand-contacted normal vector in hydrophobic interaction.
33 . The method of claim 28 , wherein the method is performed in silico.
34 . The method of claim 28 , wherein the distance-dependent potentials are predicted from a statistical set comprising occurrence frequencies of paired pharmacophores in molecular interactions.
35 - 51 . (canceled)Join the waitlist — get patent alerts
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