Peptide name : [D4K]OCN-3N

Source/Organism : Derivatives of ocellatin-3N

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 19

C-terminal modification: Not found

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Lactate dehydrogenase (LDH) assay

Assay time : Not found

Activity : LC50 : 12-20 μM

Cell line : HT-29

Cancer type : Colorectal adenocarcinoma

Other activity : Anti-bacterial activity; Anti-fungal activity

Amino acid composition bar chart :

Molecular mass : 1959.3755 Dalton

Aliphatic index : 1.436

Instability index : -16.310

Hydrophobicity (GRAVY) : 0.8895

Isoelectric point : 10.302

Charge (pH 7) : 2.7571

Aromaticity : 0.052

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

Hydrophobic/hydrophilic ratio : 1.71428571

hydrophobic moment : -1.060

Missing amino acid : C,R,W,H,Q,P,M,E,D,Y

Most occurring amino acid : K

Most occurring amino acid frequency : 3

Least occurring amino acid : F

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.2, 0.4)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C

1 : Conlon JM, et al. Antimicrobial, cytotoxic, and insulin-releasing activities of the amphibian host-defense peptide ocellatin-3N and its L-lysine-substituted analogs. J Pept Sci. 2023; 29:e3463. doi: 10.1002/psc.3463

Paper title : Antimicrobial, cytotoxic, and insulin-releasing activities of the amphibian host-defense peptide ocellatin-3N and its L-lysine-substituted analogs.

Doi : https://doi.org/10.1002/psc.3463

Abstract : The host-defense peptide ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH₂ ), first isolated from the Caribbean frog Leptodactylus nesiotus, inhibited growth of clinically relevant Gram-positive and Gram-negative bacteria as well as a strain of the major emerging yeast pathogen Candida parapsilosis. Increasing cationicity while maintaining amphipathicity by the substitution Asp4 →Lys increased potency against the microorganisms by between 4- and 16-fold (MIC ≤3 μM) compared with the naturally occurring peptide. The substitution Ala18 →Lys and the double substitution Asp4 →Lys and Ala18 →Lys had less effects on potency. The [D4K] analog also showed 2.5- to 4-fold greater cytotoxic potency against non-small-cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells (LC₅₀ values in the range of 12-20 μM) compared with ocellatin-3N but was less hemolytic to mouse erythrocytes. However, the peptide showed no selectivity for tumor-derived cells [LC₅₀  = 20 μM for human umbilical vein endothelial cells (HUVECs)]. Ocellatin-3N and [D4K]ocellatin-3N stimulated the release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥1 nM, and [A18K]ocellatin-3N, at concentrations ≥0.1 nM. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM, indicating that plasma membrane integrity had been preserved. The three peptides produced an increase in intracellular [Ca2+ ] in BRIN-BD11 cells when incubated at a concentration of 1 μM. In view of its high insulinotropic potency and relatively low hemolytic activity, the [A18K] ocellatin analog may represent a template for the design of agents with therapeutic potential for the treatment of patients with type 2 diabetes.