Peptide name : [R/K]cT1

Source/Organism : Synthetic

Linear/Cyclic : Cyclic

Chirality : L

Peptide length: 18

C-terminal modification: Cyclic

N-terminal modification : Cyclized

Non-natural peptide information:

Assay type : Resazurin dye assay

Assay time : 24-h

Activity : CC50 = 4.3 ± 0.3 µM

Cell line : WM164

Cancer type : Skin Cancer

Other activity : Host Defense Peptide

Amino acid composition bar chart :

Molecular mass : 2185.742 Dalton

Aliphatic index : 0.377

Instability index : -17.772

Hydrophobicity (GRAVY) : -0.344

Isoelectric point : 9.5096

Charge (pH 7) : 5.7125

Aromaticity : 22.22

Molar extinction coefficient (cysteine, cystine): (4, 2)

Hydrophobic/hydrophilic ratio : 1.25

hydrophobic moment : -0.271

Missing amino acid : A,D,E,H,L,M,N,P,Q,R,S,T

Most occurring amino acid : K

Most occurring amino acid frequency : 6

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (33., 11., 33.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)CCCCN)C(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)O

1 : Vernen F, et al. Cyclic Analogues of Horseshoe Crab Peptide Tachyplesin I with Anticancer and Cell Penetrating Properties. ACS Chem Biol. 2019; 14:2895-2908. doi: 10.1021/acschembio.9b00782

Paper title : Cyclic Analogues of Horseshoe Crab Peptide Tachyplesin I with Anticancer and Cell Penetrating Properties.

Doi : https://doi.org/10.1021/acschembio.9b00782

Abstract : Tachyplesin-I (TI) is a host defense peptide from the horseshoe crab Tachypleus tridentatus that has outstanding potential as an anticancer therapeutic lead. Backbone cyclized TI (cTI) has similar anticancer properties to TI but has higher stability and lower hemolytic activity. We designed and synthesized cTI analogues to further improve anticancer potential and investigated structure-activity relationships based on peptide-membrane interactions, cellular uptake, and anticancer activity. The membrane-binding affinity and cytotoxic activity of cTI were found to be highly dependent on peptide hydrophobicity and charge. We describe two analogues with increased selectivity toward melanoma cells and one analogue with the ability to enter cells with high efficacy and low toxicity. Overall, the structure-activity relationship study shows that cTI can be developed as a membrane-active antimelanoma lead, or be employed as a cell penetrating peptide scaffold that can target and enter cells without damaging their integrity.