Peptide name : HB43-mut2

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 13

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : AlamarBlue assay

Assay time : 24-h

Activity : IC50 = 50 ± 3 μM

Cell line : HT-29

Cancer type : Colon Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 1456.9 Dalton

Aliphatic index : 1.730

Instability index : -16.892

Hydrophobicity (GRAVY) : 0.8923

Isoelectric point : 10.477

Charge (pH 7) : 3.7561

Aromaticity : 7.692

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

Hydrophobic/hydrophilic ratio : 2.25

hydrophobic moment : 1.9614

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

Most occurring amino acid : L

Most occurring amino acid frequency : 5

Least occurring amino acid : F

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (92., 0, 46.)

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

1 : Herrera-León C, et al. The Influence of Short Motifs on the Anticancer Activity of HB43 Peptide. Pharmaceutics. 2022; 14:(unknown pages). doi: 10.3390/pharmaceutics14051089

Paper title : The Influence of Short Motifs on the Anticancer Activity of HB43 Peptide.

Doi : https://doi.org/10.3390/pharmaceutics14051089

Abstract : Despite the remarkable similarity in amino acid composition, many anticancer peptides (ACPs) display significant differences in terms of activity. This strongly suggests that particular relative dispositions of amino acids (motifs) play a role in the interaction with their biological target, which is often the cell membrane. To better verify this hypothesis, we intentionally modify HB43, an ACP active against a wide variety of cancers. Sequence alignment of related ACPs by ADAPTABLE web server highlighted the conserved motifs that could be at the origin of the activity. In this study, we show that changing the order of amino acids in such motifs results in a significant loss of activity against colon and breast cancer cell lines. On the contrary, amino acid substitution in key motifs may reinforce or weaken the activity, even when the alteration does not perturb the amphipathicity of the helix formed by HB43 on liposomes mimicking their surface. NMR and MD simulations with different membrane models (micelles, bicelles, and vesicles) indicate that the activity reflects the insertion capability in cancer-mimicking serine-exposing membranes, supported by the insertion of N-terminal phenylalanine in the FAK motif and the anchoring to the carboxylate of phosphatidylserine by means of arginine side chains.