Peptide name : Cyclic [W(RW)4 ]-Dox

Source/Organism : Not found

Linear/Cyclic : Cyclic

Chirality : L

Peptide length: 9

C-terminal modification: Cyclic

N-terminal modification : Free

Non-natural peptide information: None

Assay type : MTT/MTS assay

Assay time : 72 to 120h

Activity : 62-73% inhibition of cell proliferation at 1 µM

Cell line : CCRF-CEM

Cancer type : Leukemia cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1573.8076 Dalton

Aliphatic index : 0

Instability index : 263.466

Hydrophobicity (GRAVY) : -2.5

Isoelectric point : 12

Charge (pH 7) : 3.7601

Aromaticity : 0.555

Molar extinction coefficient (cysteine, cystine): (27500, 27500)

Hydrophobic/hydrophilic ratio : 1.25

hydrophobic moment : -0.3

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

Most occurring amino acid : W

Most occurring amino acid frequency : 5

Least occurring amino acid : R

Least occurring amino acid frequency : 4

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

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

1 : Nasrolahi Shirazi A, et al. Design and biological evaluation of cell-penetrating peptide-doxorubicin conjugates as prodrugs. Mol Pharm. 2013; 10:488-99. doi: 10.1021/mp3004034

Paper title : Design and biological evaluation of cell-penetrating peptide-doxorubicin conjugates as prodrugs.

Doi : https://doi.org/10.1021/mp3004034

Abstract : Doxorubicin (Dox) is a hydrophilic anticancer drug that has short retention time due to the efficient efflux in some cancer cells (e.g., ovarian adenocarcinoma SK-OV-3). Cyclic [W(RW)(4)] and the corresponding linear peptide (RW)(4) were conjugated with Dox through an appropriate linker to afford cyclic [W(RW)(4)]-Dox and linear (RW)(4)-Dox conjugates to enhance the cellular uptake and cellular retention of the parent drug for sustained anticancer activity. Comparative antiproliferative assays between covalent (cyclic [W(RW)(4)]-Dox and linear (RW)(4)-Dox) and the corresponding noncovalent physical mixtures of the peptides and Dox were performed. Cyclic [W(RW)(4)]-Dox inhibited the cell proliferation of human leukemia (CCRF-CEM) (62-73%), ovarian adenocarcinoma (SK-OV-3) (51-74%), colorectal carcinoma (HCT-116) (50-67%), and breast carcinoma (MDA-MB-468) (60-79%) cells at a concentration of 1 μM after 72-120 h of incubation. Cyclic [W(RW)(4)]-Dox exhibited higher antiproliferative activity than linear (RW)(4)-Dox in all cancer cells with the highest activity observed after 72 h. Flow cytometry analysis showed 3.6-fold higher cellular uptake of cyclic [W(RW)(4)]-Dox than Dox alone in SK-OV-3 cells after 24 h incubation. The cellular hydrolysis study showed that 99% of cyclic [W(RW)(4)]-Dox was hydrolyzed intracellularly within 72 h and released Dox. These data suggest that cyclic [W(RW)(4)]-Dox can be used as a potential prodrug for improving the cellular delivery and retention of Dox.