LyP-1 peptide

LyP-1 (CGNKRTRGC), a cyclic phage-displayed nonapeptide was identified as a tumor lymphatic vessel homing peptide. LyP-1 accumulated in the tumor lymphatics but not the tumor blood vessels of several tumor xenograft models including osteosarcomas, prostate and breast cancers, and metastatic lymph nodes of the vascular endothelial growth factor C (VEGF-C) overexpressing MDA-MB-435 tumors. In addition, LyP-1 recognizes the hypoxic tumor lesions. LyP-1 is a unique peptide due to its tumor penetrating ability and the inbuilt antitumor activity. LyP-1 was internalized and inhibited the MDA-MB-435 tumor cell growth in a dose dependent manner with an IC50 of approximately 66 uM. This effect was LyP-1 specific and no effect on cell viability was detected when cells were treated with the control peptides (CRVRTRSGC, CGEKRTRGC). Later the cell surface associated mitochondrial protein p32/gC1qR was identified as the LyP-1 interacting partner expressed by tumor cells and tumor-associated macrophages that are often incorporated into the walls of tumor lymphatic vessels. p32 is expressed in several tumor types as well as in atherosclerotic lesions. The LyP-1 peptide has been used in several applications for tumor targeted delivery of imaging and therapeutic agents. Timur et al. elucidated the interaction between LyP-1 and p32 by generating alanine scan derivatives of the LyP-1 peptide followed by interaction studies using molecular docking and Molecular Mechanics Poisson–Boltzmann Surface Area (MM–PBSA). The structureactivity relationship data generated by alanine-scan thermodynamics revealed 3Asn, 4Lys, 5Arg, and 7Arg as the most essential amino acids responsible for the p32 binding. The shortened variant of LyP-1 (truncated LyP-1; tLyP-1) with the highest tumor penetration activity conferred by its exposed CendR internalizing domain is reviewed under the tumor penetrating peptides.