Peptide name : KHH

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 15

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 72-h

Activity : IC50 = 5.20 ± 0.71 µM

Cell line : HMLER

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 1655.0377 Dalton

Aliphatic index : 1.953

Instability index : 6.24

Hydrophobicity (GRAVY) : 1.2133

Isoelectric point : 8.7642

Charge (pH 7) : 0.9335

Aromaticity : 6.666

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

Hydrophobic/hydrophilic ratio : 4

hydrophobic moment : -0.313

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

Most occurring amino acid : L

Most occurring amino acid frequency : 7

Least occurring amino acid : K

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (66., 13., 53.)

SMILES Notation: CC(C)C[C@H](NC(=O)CN)C(=O)N[C@@H](CC(C)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](Cc1c[nH]cn1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O

1 : Chen CH, et al. Integrated Design of a Membrane-Lytic Peptide-Based Intravenous Nanotherapeutic Suppresses Triple-Negative Breast Cancer. Adv Sci (Weinh). 2022; 9:e2105506. doi: 10.1002/advs.202105506

Paper title : Integrated Design of a Membrane-Lytic Peptide-Based Intravenous Nanotherapeutic Suppresses Triple-Negative Breast Cancer.

Doi : https://doi.org/10.1002/advs.202105506

Abstract : Membrane-lytic peptides offer broad synthetic flexibilities and design potential to the arsenal of anticancer therapeutics, which can be limited by cytotoxicity to noncancerous cells and induction of drug resistance via stress-induced mutagenesis. Despite continued research efforts on membrane-perforating peptides for antimicrobial applications, success in anticancer peptide therapeutics remains elusive given the muted distinction between cancerous and normal cell membranes and the challenge of peptide degradation and neutralization upon intravenous delivery. Using triple-negative breast cancer as a model, the authors report the development of a new class of anticancer peptides. Through function-conserving mutations, the authors achieved cancer cell selective membrane perforation, with leads exhibiting a 200-fold selectivity over non-cancerogenic cells and superior cytotoxicity over doxorubicin against breast cancer tumorspheres. Upon continuous exposure to the anticancer peptides at growth-arresting concentrations, cancer cells do not exhibit resistance phenotype, frequently observed under chemotherapeutic treatment. The authors further demonstrate efficient encapsulation of the anticancer peptides in 20 nm polymeric nanocarriers, which possess high tolerability and lead to effective tumor growth inhibition in a mouse model of MDA-MB-231 triple-negative breast cancer. This work demonstrates a multidisciplinary approach for enabling translationally relevant membrane-lytic peptides in oncology, opening up a vast chemical repertoire to the arms race against cancer.