Peptide name : Ascaphin-8 [T16A]

Source/Organism : Synthetic construct

Linear/Cyclic : Linear

Chirality : L

Peptide length: 19

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : Not found

Cancer type : Liver cancer

Other activity : Anti-microbial activity

Amino acid composition bar chart :

Molecular mass : 1989.4461 Dalton

Aliphatic index : 1.336

Instability index : -13.357

Hydrophobicity (GRAVY) : 0.8684

Isoelectric point : 10.001

Charge (pH 7) : 2.7572

Aromaticity : 0.105

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

Hydrophobic/hydrophilic ratio : 2.8

hydrophobic moment : -0.362

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

Most occurring amino acid : K

Most occurring amino acid frequency : 4

Least occurring amino acid : D

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.6, 0.1, 0.4)

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

1 : Conlon JM, et al. Design of potent, non-toxic antimicrobial agents based upon the naturally occurring frog skin peptides, ascaphin-8 and peptide XT-7. Chem Biol Drug Des. 2008; 72:58-64. doi: 10.1111/j.1747-0285.2008.00671.x

Paper title : Design of potent, non-toxic antimicrobial agents based upon the naturally occurring frog skin peptides, ascaphin-8 and peptide XT-7.

Doi : https://doi.org/10.1111/j.1747-0285.2008.00671.x

Abstract : The frog skin peptides, ascaphin-8 (GFKDLLKGAAKALVKTVLF.NH(2)) and XT-7 (GLLGPLLKIAAKVGSNLL.NH(2)), show broad-spectrum antimicrobial activity but their therapeutic potential is limited by toxicity against mammalian cells. Circular dichroism spectra demonstrate that the peptides adopt an amphipathic alpha-helical conformation in a membrane-mimetic solvent. This study has investigated the cytolytic properties of analogs containing selected amino acid substitutions that increase cationicity while maintaining amphipathicity. Substitutions at Ala(10), Val(14), and Leu(18) in ascaphin-8 by either L-Lys or D-Lys produced peptides that retained antimicrobial activity against the bacteria Escherichia coli and Staphylococcus aureus and the opportunistic yeast pathogen, Candida albicans but showed appreciably reduced toxicities (>10-fold) against human erythrocytes, HepG2 hepatoma-derived cells, and L929 fibroblasts. The improved therapeutic index of the L-Lys(18) and D-Lys(18) analogs correlated with a decrease in % helicity and in effective hydrophobicity. Substitution of Gly(4) by L-Lys in XT-7 produced an analog with high potency against micro-organisms (MIC < or = 25 microM) but low cytolytic activity against erythrocytes (LD(50) > 500 microM) and this increase in therapeutic index also correlated with decreased helicity and hydrophobicity. Analogs of XT-7 with increased cationicity, containing multiple substitutions by L-Lys, not only displayed increased antimicrobial potencies, particularly against Candida albicans (MIC < or = 6 microM), but also increased hemolytic activities.