Peptide name : PMAP-NC

Source/Organism : Synthetic Analgog of PMAP-24

Linear/Cyclic : Linear

Chirality : L

Peptide length: 23

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTT assay

Assay time : 4-h

Activity : IC50 = 7.1 μM

Cell line : A-549

Cancer type : Lung Cancer

Other activity : Antimicrobial

Amino acid composition bar chart :

Molecular mass : 2931.6129 Dalton

Aliphatic index : 1.521

Instability index : 56.6304

Hydrophobicity (GRAVY) : 0.2609

Isoelectric point : 12

Charge (pH 7) : 4.7592

Aromaticity : 13.04

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

Hydrophobic/hydrophilic ratio : 1.875

hydrophobic moment : -0.153

Missing amino acid : A,C,E,G,H,M,N,S,T,Y

Most occurring amino acid : R

Most occurring amino acid frequency : 4

Least occurring amino acid : D

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (26., 13., 56.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)CC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)C)C(C)C)C(C)C)C(C)C

1 : Lee H, et al. Rationally designed PMAP-23 derivatives with enhanced bactericidal and anticancer activity based on the molecular mechanism of peptide-membrane interactions. Amino Acids. 2023; 55:1013-1022. doi: 10.1007/s00726-023-03290-5

Paper title : Rationally designed PMAP-23 derivatives with enhanced bactericidal and anticancer activity based on the molecular mechanism of peptide-membrane interactions.

Doi : https://doi.org/10.1007/s00726-023-03290-5

Abstract : Antimicrobial peptides (AMPs) are a crucial component of the natural defense system that the host employs to protect itself against invading pathogens. PMAP-23, a cathelicidin-derived AMP, has potent and broad-spectrum antimicrobial activity. Our earlier studies led us to hypothesize that PMAP-23 adopts a dynamic helix-hinge-helix structure, initially attaching to membrane surfaces through the N-helix and subsequently inserting the C-helix into the lipid bilayer. Here, we rationally designed PMAP-NC with increased amphipathicity and hydrophobicity in the N- and C-helix, respectively, based on the hypothesis of the interaction of PMAP-23 with membranes. Compared to the parental PMAP-23, PMAP-NC showed two-eightfold improved bactericidal activity against both Gram-positive and Gram-negative strains with fast killing kinetics. Fluorescence studies demonstrated that PMAP-NC largely disrupted membrane integrity, indicating that efficiency and kinetics of bacterial killing are associated with the membrane permeabilization. Interestingly, PMAP-NC exhibited much better anticancer activity against tumor cells than PMAP-23 but displayed low hemolytic activity against human erythrocytes. Collectively, our findings suggest that PMAP-NC, with the structural arrangement of an amphipathic helix-hinge-hydrophobic helix that plays a critical role in rapid and efficient membrane permeabilization, can be an attractive candidate for novel antimicrobial and/or anticancer drugs.