Peptide name : Sur-X

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 35

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTT assay

Assay time : Not Available

Activity : Not Available

Cell line : HCT-15

Cancer type : Colon Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 4409.1003 Dalton

Aliphatic index : 0.251

Instability index : 99.8086

Hydrophobicity (GRAVY) : -1.66

Isoelectric point : 11.273

Charge (pH 7) : 8.8291

Aromaticity : 11.42

Molar extinction coefficient (cysteine, cystine): (2, 1)

Hydrophobic/hydrophilic ratio : 0.5909

hydrophobic moment : -0.105

Missing amino acid : V

Most occurring amino acid : R

Most occurring amino acid frequency : 8

Least occurring amino acid : Y

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (25., 19., 22.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)O)[C@@H](C)O)[C@@H](C)O

1 : Fang W, et al. Sur-X, a novel peptide, kills colorectal cancer cells by targeting survivin-XIAP complex. J Exp Clin Cancer Res. 2020; 39:82. doi: 10.1186/s13046-020-01581-3

Paper title : Sur-X, a novel peptide, kills colorectal cancer cells by targeting survivin-XIAP complex.

Doi : https://doi.org/10.1186/s13046-020-01581-3

Abstract : BACKGROUND: Survivin and XIAP are two important members of the inhibitor of apoptosis protein family and have been considered as potential targets for cancer treatment due to their overexpression in large variety of cancers including colorectal cancer. It has been reported that survivin and XIAP can synergistically inhibit apoptosis by forming survivin-XIAP complex. In this study, we aimed to design a peptide that targets the survivin-XIAP complex and elucidate its anticancer mechanisms in colorectal cancer cells. METHODS: We designed and synthetized Sur-X, the peptide targeting survivin-XIAP complex. The anticancer effects of Sur-X were evaluated both in vitro and in vivo. The underlying molecular mechanisms were also investigated. RESULTS: Sur-X exhibited potent inhibitory effects on four colorectal cancer cell lines HCT116, HCT15, RKO and HT29, but not on human peritoneal mesothelial cell line HMrSV5. Mechanistically, Sur-X induced Caspase 9-dependent intrinsic apoptosis in colorectal cancer cells by disrupting the survivin-XIAP complex and subsequently destabilizing survivin and XIAP. Interestingly, we found that Sur-X can also promote necroptosis. It was demonstrated that Sur-X destroyed the interaction between XIAP and TAB1 in the XIAP-TAB1-TAK1 complex, leading to the instability of TAK1, an endogenous necroptosis inhibitor. Subsequently, the accelerated degradation of TAK1 attenuated its inhibition on necroptosis in colorectal cancer cells. Moreover, knockdown of TAK1 restored the sensitivity of TAB1-overexpressing colorectal cancer cells to Sur-X-induced necroptosis. The in vivo pro-apoptotic effect of Sur-X was confirmed by the enhanced TUNEL staining and the decreased expression of survivin and XIAP in tumor tissues from xenograft mouse models. In addition, extensive necrosis and weaker MLKL expression in xenografts provided evidence for the in vivo pro-necroptotic effect of Sur-X. CONCLUSIONS: Peptide Sur-X exhibits strong pro-apoptotic and pro-necroptotic effects in colorectal cancer cells and has a high clinical translation potential in the treatment of colorectal cancer.