Peptide name : Crabrolin-4R

Source/Organism : Synthetic Analog of Crabrolin

Linear/Cyclic : Linear

Chirality : L

Peptide length: 13

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 = 20.26 μM

Cell line : MCF-7

Cancer type : Breast Cancer

Other activity : Antimicrobial

Amino acid composition bar chart :

Molecular mass : 1539.9488 Dalton

Aliphatic index : 1.8

Instability index : 28.2846

Hydrophobicity (GRAVY) : 1.0769

Isoelectric point : 12

Charge (pH 7) : 2.7591

Aromaticity : 7.692

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

Hydrophobic/hydrophilic ratio : 2.25

hydrophobic moment : -0.248

Missing amino acid : C,D,E,G,H,M,N,Q,S,W,Y

Most occurring amino acid : L

Most occurring amino acid frequency : 3

Least occurring amino acid : F

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (38., 7.6, 61.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)O)[C@@H](C)O)C(C)C)[C@@H](C)CC

1 : Yao A, et al. A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity. Int J Mol Sci. 2023; 24:(unknown pages). doi: 10.3390/ijms241914472

Paper title : A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity.

Doi : https://doi.org/10.3390/ijms241914472

Abstract : Antimicrobial peptides have gradually attracted interest as promising alternatives to conventional agents to control the worldwide health threats posed by antibiotic resistance and cancer. Crabrolin is a tridecapeptide extracted from the venom of the European hornet (Vespa crabro). Its antibacterial and anticancer potentials have been underrated compared to other peptides discovered from natural resources. Herein, a series of analogs were designed based on the template sequence of crabrolin to study its structure-activity relationship and enhance the drug's potential by changing the number, type, and distribution of charged residues. The cationicity-enhanced derivatives were shown to have improved antibacterial and anticancer activities with a lower toxicity. Notably, the double-arginine-modified product, crabrolin-TR, possessed a potent capacity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 4 μM), which was around thirty times stronger than the parent peptide (MIC = 128 μM). Furthermore, crabrolin-TR showed an in vivo treatment efficacy in a Klebsiella-pneumoniae-infected waxworm model and was non-toxic under its maximum MBC value (MIC = 8 μM), indicating its therapeutic potency and better selectivity. Overall, we rationally designed functional peptides by progressively increasing the number and distribution of charged residues, demonstrating new insights for developing therapeutic molecules from natural resources with enhanced properties, and proposed crabrolin-TR as an appealing antibacterial and anticancer agent candidate for development.