Peptide name : Loop1-PS2Aa

Source/Organism : Parasporin-2Aa1

Linear/Cyclic : Linear

Chirality : L

Peptide length: 11

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : Sulforhodamine B assay

Assay time : 48-h

Activity : EC50 = 23.76 ± 1.25 µM

Cell line : SW-480

Cancer type : Colorectal Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 1296.3844 Dalton

Aliphatic index : 0.354

Instability index : -0.3818

Hydrophobicity (GRAVY) : -1.154

Isoelectric point : 6.0007

Charge (pH 7) : -0.2391

Aromaticity : 18.18

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

Hydrophobic/hydrophilic ratio : 0.5714

hydrophobic moment : 0.4272

Missing amino acid : C,D,G,H,I,L,M,Q,R,S,W

Most occurring amino acid : N

Most occurring amino acid frequency : 3

Least occurring amino acid : E

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (27., 36., 36.)

SMILES Notation: CC(C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(N)=O)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)O

1 : Cruz J, et al. Computational study, synthesis and evaluation of active peptides derived from Parasporin-2 and spike protein from Alphacoronavirus against colorectal cancer cells. Biosci Rep. 2021; 41:(unknown pages). doi: 10.1042/BSR20211964

Paper title : Computational study, synthesis and evaluation of active peptides derived from Parasporin-2 and spike protein from Alphacoronavirus against colorectal cancer cells.

Doi : https://doi.org/10.1042/BSR20211964

Abstract : Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and β-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 µM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.