Table 7.
Cancer-Targeting Peptides Isolated from OBOC Libraries Using Cultured Cells as the Target
| Cancer Type | Cell Line used for Selectiona |
Peptide Sequenceb,c,d,e,f | Cellular Receptor |
Applications and Notes |
|---|---|---|---|---|
| Breast Cancer | MDA-MB-231 |
cdGLGBNc332 (LXY1) cdGTyr(3-NO2)GBNc (LXY3)332 |
α3β1 |
Imaging applications: LXY1 peptide-biotin-streptavidin-Cy5.5 used for near-infrared imaging of U-87MG tumors in mice.333 LXY3 peptide-biotin-streptavidin-Cy5.5 used for near-infrared imaging of orthotopic MDA-MB-231 tumors. Note: LXY3 was identified from a focused peptide library based on the LXY1 sequence. |
| Leukemia | Jurkat | LTGpLDI334 | α4β1 | |
| Ovarian Cancer | CaOV-3, SKOV-3, OVCAR-3, & ES-2 |
cLDWDLIc335 cDGLGDDc335 cDGWGPNc335 |
α3 (DGLG peptide) | |
| ES-2 | cdGHCitGPQc336 (OA02) | α3 |
Therapeutic Applications: OA02 peptide displayed on the surface of paclitaxel loaded micelles improves efficacy in two ovarian cancer models compared to the non-targeted paclitaxel or paclitaxel-micelles.337 Imaging applications: A OA02 peptide-biotin-streptavidin-Cy5.5 and peptide-Cy5.5 have been used for near-infrared imaging of ES-2 tumors in mice.336 [64Cu] DOTA-OA02 peptide was used for microPET imaging of ES-2 tumor and SKOV3 metastatic lesion in mice.18 |
|
| SKOV-3 |
cdG-Cha-G-HCit-Qc18 cdG-Chg-G-Hyp-Nc18 cdG-HCit-GPQc18 cdGIGPQc18 cdGLGQ-Bta-c18 cdG-Phe-GP-Cha-c18 cdG-Tyr-GI-Pra-c18 |
Note: The peptides bind multiple cancer cell lines but most also bind a normal human lung epithelial cell line. | ||
| Lung Cancer | A549 | cNGQGEQc338 (pA) | α3β1 | Note: A consensus sequence of NGXG was observed for most positive hits. |
| HI650 | cNleDNleTHyprc339 (pM2) | α4β1 | ||
| Prostate | DU145 | LNIVSVNGRHX85 (RU-1) DNRIRLQAKXX85 (RX-1) |
||
| kmviywkag340 (RZ-3) kikmviswkg340 (HYD-1) |
α3β1341 (RZ-3) α6β1 and α3β1341 (HYD-1) |
Functional Peptide Activity: Free HYD-1 peptide induced cell death in multiple myeloma cells and inhibited H929 tumor growth in mice when injected i.p.342 RZ-3 inhibited random haptotaxis of PC3N cells on lamin-5.341 HYD-1 blocked random haptotaxis and inhibited invasion of PC3N cells on lamin-5.341 HYD-1 also inhibited adhesion of H929 cells to fibronectin mediated by α4β1.342 | ||
| LNCaP | QMARIPKRLARH50 | Note: The peptide binds to other epithelial derived cancer cell lines and can be used to label LNCaP cells spiked into whole blood. | ||
| Bladder Cancer | 5637 | cQDGRMGFc343 (PLZ4) | Imaging applications: Near-infrared imaging of human bladder tumor-bearing mice was performed with a peptide-biotin-SA-Cy5.5 conjugate. |
a
All cell lines are of human origin.
b
Cysteine residues that form disulfide bonds are indicated in bold.
c
Lowercase indicates d-amino acids.
d
Abbreviations for unnatural amino acids are as follows: B = hydroxyproline, Cha = cyclohexylalanine, Chg = α-cyclohexylglycine, HCit = homocitrulline, Hyo = hydroxyproline, Bta = benzothioenylalanine, Phe = 4-methylphenylalanine, Pra = propargylglycine, Tyr = 3-nitrotyrosine, and Nle = norleucine.
e
Common peptide names that have been used in the literature are indicated in parentheses next to the peptide sequence.
f
Peptides clustered in the same cell in this table were isolated in the same selection experiment.