Peptide name : Longicalycinin A linear analogue 14

Source/Organism : Synthetic Analogue of Longicalycinin A

Linear/Cyclic : Linear

Chirality : L

Peptide length: 5

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 = 9.12 ± 0.0042 µg/ml

Cell line : HT-29

Cancer type : Colorectal Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 685.8089 Dalton

Aliphatic index : 0.78

Instability index : 8

Hydrophobicity (GRAVY) : 1.3

Isoelectric point : 5.95

Charge (pH 7) : -0.0425

Aromaticity : 60

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

Hydrophobic/hydrophilic ratio : 4

hydrophobic moment : 0.0611

Missing amino acid : A,C,D,E,G,H,I,K,M,N,Q,R,S,T,V,W

Most occurring amino acid : F

Most occurring amino acid frequency : 2

Least occurring amino acid : P

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (20, 20, 80)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1)C(=O)O

1 : Gholibeikian M, et al. Structure-activity relationship studies of Longicalcynin A analogues, as anticancer cyclopeptides. Chem Biol Interact. 2020; 315:108902. doi: 10.1016/j.cbi.2019.108902

Paper title : Structure-activity relationship studies of Longicalcynin A analogues, as anticancer cyclopeptides.

Doi : https://doi.org/10.1016/j.cbi.2019.108902

Abstract : Cancer has emerged as the main cause of the highest rate of mortality in the world. Drugs used in cancer, although, show some beneficial effects on cancerous organs, demonstrate side effects on other normal tissues. On the other hand, anticancer peptides, being effective on target tissues, should be safe and less harmful on healthy organs, since peptides have several advantages, i.e., high activity, specificity, affinity, being less immunogenic and not accumulate in the body. In the present work, analogues of Longicalcynin A, a naturally occurring anticancer cyclopeptide, were synthesized and evaluated their cytotoxicity in order to gain information from structure-activity relationships of the such cyclopeptides which may lead to find novel and safer anticancer peptide compound(s) to be used in clinic. Peptides were prepared by the solid-phase peptide synthesis method using trityl-resin. Peptide cyclization was performed in liquid phase. To study anticancer activity of the peptide analogues of Longicalycinin A, several methods including MTT, flow cytometry analysis and Lysosomal membrane integrity assay were employed using two cell lines HepG2 and HT-29. Fibroblast cells were used to control the safety of the synthesized cyclopeptides on normal cells. Two cyclopeptides 11 and 17 with the sequences of cyclo-(Thr-Val-Pro-Phe-Ala) and cyclo-(Phe-Ser-Pro-Phe-Ala), respectively were cytotoxic against the colon as well as hepatic cancer cells with safety profile against fibroblast cells, probably with the mechanism of apoptosis as lysosomal membrane integrity damaged. These cyclopeptides showed to be more favorable compounds better than Longicalycinin A and good candidates to develop cyclopeptides as anticancer agents.