Peptide name : KM8

Source/Organism : Synthetic derivative of Mastoparan

Linear/Cyclic : Linear

Chirality : L

Peptide length: 18

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : Not Available

Assay time : Not Available

Activity : Not Available

Cell line : Not Available

Cancer type : Not Available

Other activity : Antimicrobial

Amino acid composition bar chart :

Molecular mass : 1962.5518 Dalton

Aliphatic index : 1.955

Instability index : -3.4389

Hydrophobicity (GRAVY) : 0.8889

Isoelectric point : 10.602

Charge (pH 7) : 4.7551

Aromaticity : 0

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

Hydrophobic/hydrophilic ratio : 2

hydrophobic moment : -1.339

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

Most occurring amino acid : L

Most occurring amino acid frequency : 6

Least occurring amino acid : N

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (83., 5.5, 44.)

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

1 : Zhang C, et al. Plasma metabolites-based design of long-acting peptides and their anticancer evaluation. Int J Pharm. 2023; 631:122483. doi: 10.1016/j.ijpharm.2022.122483

Paper title : Plasma metabolites-based design of long-acting peptides and their anticancer evaluation.

Doi : https://doi.org/10.1016/j.ijpharm.2022.122483

Abstract : Antimicrobial peptides (AMPs) are generally small cationic amphipathic peptides, which are thought to be ideal antineoplastic agents, owing to their favorable selectivity to cancer cells and the ability to overcome drug-resistance. In this study, an anticancer AMP (Mastoparan (INLKALAALAKKIL-NH2)) was selected as the lead compound and a series of Mastoparan derivatives were designed. Preliminary studies verified that an analogue of Mastoparan, KM8 (KLLKINLKALAALAKKIL-NH2), exhibited prominent selective antitumor effects. Instead, it presents a significant defect of metabolic instability, with a half-life in plasma of only about 0.5 h. Metabolite profiling of KM8 was performed and indicated the structure ₉AL₁₀ in peptide sequence could be the fragile site for KM8. Thus, the Aib (unnatural amnio acid) was employed to substitute the ₉Ala residue in KM8, and generating a long-acting KM8 derivative, namely KM8-Aib. Further investigations revealed KM8-Aib possessed higher metabolic stability, more potent anticancer activity in vitro & in vivo, and lower toxicity. Therefore, KM8-Aib is suggested be a potential antimalignant agent that worthy of more in-depth study.