Peptide name : Dex-(KW)3

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 6

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : MTT/MTS assay

Assay time : Not found

Activity : At 10 µM 35-40% viablity

Cell line : MCF-7

Cancer type : Breast cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 961.1619 Dalton

Aliphatic index : 0

Instability index : 8.3333

Hydrophobicity (GRAVY) : -2.4

Isoelectric point : 10.302

Charge (pH 7) : 2.7571

Aromaticity : 0.5

Molar extinction coefficient (cysteine, cystine): (16500, 16500)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -0.471

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

Most occurring amino acid : K

Most occurring amino acid frequency : 3

Least occurring amino acid : K

Least occurring amino acid frequency : 3

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0, 0.5)

SMILES Notation: NCCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O

1 : Zhong J and Chau Y. Synthesis, characterization, and thermodynamic study of a polyvalent lytic peptide-polymer conjugate as novel anticancer agent. Bioconjug Chem. 2010; 21:2055-64. doi: 10.1021/bc1002899

Paper title : Synthesis, characterization, and thermodynamic study of a polyvalent lytic peptide-polymer conjugate as novel anticancer agent.

Doi : https://doi.org/10.1021/bc1002899

Abstract : We designed and synthesized a new polyvalent lytic peptide-polymer conjugate as a novel chemotherapeutic agent capable of overcoming multidrug resistance. A hexapeptide (KWKWKW or (KW)₃) was designed and conjugated to dextran in multiple copies to afford a polyvalent conjugate. A robust synthesis procedure involving click chemistry and the detailed characterization of the conjugate were reported here. The conjugate Dex-(KW)₃ exhibited significantly enhanced anticancer potency in vitro by up to 500-fold compared to monomeric (KW)₃. The LC₅₀ value was comparable to that of conventional lytic peptides which have more than 20 residues. No hemolytic activity was shown by the conjugates up to 300 μM. Thermodynamic study indicated that the binding of conjugates was predominantly entropy-driven while the binding of free peptides was mainly enthalpy-driven, implying a deeper penetration of conjugate into the core of lipid bilayer. The binding affinity of conjugate to neutral membrane is much higher than that to free peptide (K(conj) ≈ 8822.9 M⁻¹, K(pep) ≈ 1884.7 M⁻¹). In binding to negatively charged membrane, the conjugate surpassed free peptides at high concentrations when the binding of free peptides became saturated. The higher binding capability, attributed to the high local concentration of peptides mounted on a polymer backbone, explains the superior anticancer activity of polyvalent Dex-(KW)₃.