Peptide name : Smac-CPP

Source/Organism : SMAC

Linear/Cyclic : Linear

Chirality : L

Peptide length: 22

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : IC50 : 132 μM

Cell line : 4T1

Cancer type : Not found

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2675.1216 Dalton

Aliphatic index : 0.531

Instability index : 237.095

Hydrophobicity (GRAVY) : -1.813

Isoelectric point : 12

Charge (pH 7) : 10.7948

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 0.57142857

hydrophobic moment : 0.2412

Missing amino acid : C,W,H,T,M,E,F,D,Y,L,N

Most occurring amino acid : R

Most occurring amino acid frequency : 10

Least occurring amino acid : P

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.1, 0.2, 0.1)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)N)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C

1 : Priwitaningrum DL, et al. Apoptosis-inducing peptide loaded in PLGA nanoparticles induces anti-tumor effects in vivo. Int J Pharm. 2020; 585:119535. doi: 10.1016/j.ijpharm.2020.119535

Paper title : Apoptosis-inducing peptide loaded in PLGA nanoparticles induces anti-tumor effects in vivo.

Doi : https://doi.org/10.1016/j.ijpharm.2020.119535

Abstract : Induction of apoptosis in tumor cells specifically within the complex tumor microenvironment is highly desirable to kill them efficiently and to enhance the effects of chemotherapy. Second mitochondria-derived activator of caspase (Smac) is a key pro-apoptotic pathway which can be activated with a Smac mimetic peptide. However, in vivo application of peptides is hampered by several limitations such as poor pharmacokinetics, rapid elimination, enzymatic degradation, and insufficient intracellular delivery. In this study, we developed a nanosystem to deliver a Smac peptide to tumor by passive targeting. We first synthesized a chimeric peptide that consists of the 8-mer Smac peptide and a 14-mer cell penetrating peptide (CPP) and then encapsulated the Smac-CPP into polymeric nanoparticles (Smac-CPP-NPs). In vitro, Smac-CPP-NPs were rapidly internalized by 4T1 mammary tumor cells and subsequently released Smac-CPP into the cells, as shown with fluorescence microscopy. Furthermore, Smac-CPP-NPs induced apoptosis in tumor cells, as confirmed with cell viability and caspase 3/7 assays. Interestingly, combination of Smac-CPP-NPs with doxorubicin (dox), a clinically used cytostatic drug, showed combined effects in vitro in 4T1 cells. The effect was significantly better than that of SMAC-CPP-NPs alone as well as empty nanoparticles and dox. In vivo, co-treatment with Smac-CPP-NPs and free dox reduced the tumor growth to 85%. Furthermore, the combination of Smac-CPP-NPs and free dox showed reduced proliferating tumor cells (Ki-67 staining) and increased apoptotic cells (cleaved caspase-3 staining) in tumors. In conclusion, the present study demonstrates that the intracellular delivery of Smac-mimetic peptide using nanoparticle system can be an interesting strategy to attenuate the tumor growth and to potentiate the therapeutic efficacy of chemotherapy in vivo.