Cancer-targeting peptides have short amino acid sequences designed to specifically bind to cancer cells or their microenvironment. These peptides allow targeted drug delivery, imaging, and therapy. These peptides recognize and bind to molecules overexpressed on cancer cells or tumors, such as receptors, integrins, or specific antigens.
| Peptide | Sequence | Target |
| Octreotide | DFCFDWKTCT-ol | SSTR (somatostatin receptor) |
| RC160 | DFCYDWKVCW | SSTR |
| Bombesin | YQRLGNQWAVGHLM | GRPR (Gastrin releasing peptide (GRP) receptor) |
| PSAP-peptide | DWLPK | apoptotic cascade |
| NT21MP | LGASWHRPDK CCLGYQKRPLP | CXCR4, CXCR4, stromal-derived factor receptor |
| Nef-M1 | NAACAWLEAQ | CXCR4 |
| Peptide R | RACRFFC | CXCR4 |
| Pentixafor | DY-[NMe]DOrn-R-2Nal-G | CXCR4 |
| pHLIP | ACEQNPIYWA RYADWLFTTP LLLLDLALLV DADET | pH, cell membrane |
| L-zipper peptide | VSSLESKVSS LESKVSKLES KKSKLESKVS KLESKVSSLE SK | temperature |
| ELP | VPGXG Val-Pro-Gly-Xaa-Gly repeat conjugated to RRIRPRPPRL PRPRPRPLPF PRPG https://www.ncbi.nlm.nih.gov/Structure/pdb/7TOS elastin-like polypeptide coding sequence was modified by adding a Bac cell penetrating peptide (RRIRPRPPRL PRPRP RPLPFP RPG) to the ELP’s C terminus, then further adding a p21Waf1/Cip1-derived peptide (GRKRRQTSMT DFYHSKRRLI FSKRKP, p21) or its scrambled control (RTDKIKFRKF LRSRRSQP -MYSTKRGH) to the NH2 terminus. | Temperature |
| α-MSH mimics | Modifications of the α-MSH sequence ([Ac-N]LDHDFRWGL) | MC1R, melanocortin 1 receptor |
| GZP | AGGIEFAD, NOTA–βAGGIEFD–CHO (NOTA-GZP) and biotin–β-AGGIEPD–CHO (hGZP) | granzyme B |
| cRGD | RGDDYK; The cryptic CendR motif with sequence CRGDKGPDC activates the CendR pathway specifically in tumors because it first binds to αvβ3 and αvβ5 integrins, but not in normal tissue, where it is proteolytically cleaved to generate a fragment with a C-terminal CendR motif that binds to NRP-1 and activates the CendR pathway. | αVβ3 |
| EETI 2.5 F (knottin) | GCPRPRGDNP PLTCSQDSDC LAGCVCGPNG FCG | integrins |
| NGR | CNGRC | APN (CD13) |
| SP2012 | LRRFSTMPFMF-Abu-NINNV-Abu-NF | β1 integrins |
| AARP | CTTHWGFTLC | MMP2/9 + blood vessels |
| CK | CVNHPAFAC-HTMYYHHYQHHL, GYG linker | Sonic hedgehog + VEGFR2 |
| LyP-1 | CGNKRTRGC | p32 |
| AGR | CAGRRSAYC | prostate cancer lymphatics |
| REA | CREAGRKAC, D(KLAKLAK)2-CREAGRKAC | pre-malignant tumor lymphatics |
| LSD | CLSDGKRKC | tumor lymphatics |
| iRGD | CRGDKGPDC | αVβ3+NRP-1 |
| iPhage/pen | [M13]-RQIKIWFQNRRMKWKK | cell cytoplasm |
| M2pep | YEQDPWGVKWWY | M2/TAM |
| CooP | CGLSGLGVA | MDGI |
| CLT-1 | CGLIIQKNEC | fibrosis |
| Pep-1 L | CGEMGWVRC | IL13RA2 |
| Angiopep-2 | TFFYGGSRGKRNNFKTEEY | LRP-1 |
| Angiopep-7 | TFFYGGSRGRRNNFRTEEY | - |
| FHK | FHKHKSPALSPV | tenascin-c |
| tLyP-1 | CGNKRTR | NRP-1 |
| Cilengitide | cRGDf [N-Me]V | integrins |
Legend: X in a sequence = any amino acid residue; SSTR, somatostatin receptor; GRPR, gastrin releasing peptide receptor; PSAP, presenilin-associated protein; CXCR4, stromal-derived factor receptor; pHLIP, pH low insertion peptide; ELP, elastin-like peptide; α-MSH, α-melanocyte-stimulating hormone; MC1R, melanocortin 1 receptor; GZP, granzyme B peptide; APN (CD13), aminopeptidase N; Abu, L-α-amino-n-butyric acid; MMP, metalloprotease; VEGFR2, vascular endothelial growth factor receptor 2; p32, replication protein A; NRP-1, neuropilin receptor-1; pen, penetratin; TAM, tumor-associated macrophage; MDGI, mammary-derived growth inhibitor; LRP-1, low density lipoprotein receptor-related protein-1.
Adapted from: Le Joncour V, Laakkonen P. Seek & Destroy, use of targeting peptides for cancer detection and drug delivery. Bioorg Med Chem. 2018 Jun 1;26(10):2797-2806. [ScienceDirect]
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