Peptide name : 1[dR][Pal]

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : Mix

Peptide length: 9

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 = 105 μM

Cell line : CaCo-2

Cancer type : Colorectal Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 1487.6704 Dalton

Aliphatic index : 0

Instability index : 136.177

Hydrophobicity (GRAVY) : -2.677

Isoelectric point : 12

Charge (pH 7) : 2.7601

Aromaticity : 44.44

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

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : 0.04

Missing amino acid : A,C,D,E,F,G,H,I,K,L,M,N,P,S,T,V,Y

Most occurring amino acid : W

Most occurring amino acid frequency : 4

Least occurring amino acid : r

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0, 0, 44.)

SMILES Notation: N=C(N)NCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)O

1 : Cárdenas-Martínez KJ, et al. Evaluating the In Vitro Activity and Safety of Modified LfcinB Peptides as Potential Colon Anticancer Agents: Cell Line Studies and Insect-Based Toxicity Assessments. ACS Omega. 2023; 8:37948-37957. doi: 10.1021/acsomega.3c03455

Paper title : Evaluating the In Vitro Activity and Safety of Modified LfcinB Peptides as Potential Colon Anticancer Agents: Cell Line Studies and Insect-Based Toxicity Assessments.

Doi : https://doi.org/10.1021/acsomega.3c03455

Abstract : Anticancer peptides are increasingly being considered as alternative treatments for cancer due to their potency, selectivity, and low toxicity. Previously, the peptide LfcinB (21-25)_Pal showed in vitro anticancer effects against the Caco-2 colon cancer cell line (half-maximal inhibitory concentration (IC₅₀): 86 μM). In this study, we developed modifications to the peptide sequence to increase its anticancer activity. Sequence modifications were made such as the inclusion of amino hexanoic acid (Ahx), N-terminal biotinylation, acetylation, and substitutions of Orn for Arg and/or d-Arg by l-Arg. The molecules were synthesized using manual solid-phase peptide synthesis (SPPS), and their synthetic feasibility (SAScore) ranged from 6.2 to 7.6. The chromatographic purities of the synthesized peptides were greater than 89%. We found that Ahx-RWQWRWQWR and RWQWRWQW-Orn showed activity against both Caco-2 and HT-29 cell lines and decreased IC₅₀ values by approx. 50% in Caco-2 cells (IC₅₀: 40 μM) when compared to the parent peptide RWQWRWQWR. Moreover, the modified peptides demonstrated lower hemolytic effects, with values <10% at 200 μg/mL. Toxicity was assessed using the Galleria mellonella model and the half-maximal lethal dose (LD₅₀) for the best peptides was >100 mg/kg, indicating that their toxicity is classified as moderately toxic or lower. In contrast, cisplatin showed an LD₅₀ of 13 mg/Kg. The designed anticancer peptides presented good in vitro activity and low toxicity, making them promising molecules for future drug development studies.