Peptide name : mt_T18S/L22 W/P27A

Source/Organism : MDM4

Linear/Cyclic : Linear

Chirality : L

Peptide length: 12

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information: None

Assay type : MTT/MTS assay

Assay time : Not found

Activity : IC50 : 27 µM

Cell line : MCF-7

Cancer type : Breast cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1510.6443 Dalton

Aliphatic index : 0.733

Instability index : 18.1417

Hydrophobicity (GRAVY) : -0.466

Isoelectric point : 4.4267

Charge (pH 7) : -2.155

Aromaticity : 0.25

Molar extinction coefficient (cysteine, cystine): (11000, 11000)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -1.476

Missing amino acid : C,R,H,Q,T,P,M,I,Y,N,V,G

Most occurring amino acid : E

Most occurring amino acid frequency : 2

Least occurring amino acid : F

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.2, 0.4)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)O

1 : Fang Y, et al. Design of p53-derived peptides with cytotoxicity on breast cancer. Amino Acids. 2014; 46:2015-24. doi: 10.1007/s00726-014-1750-y

Paper title : Design of p53-derived peptides with cytotoxicity on breast cancer.

Doi : https://doi.org/10.1007/s00726-014-1750-y

Abstract : The tumor suppressor p53 plays essential role in conserving stability by preventing genome mutation, which is inactivated naturally by its negative regulator MDM2. Thus, targeting p53-MDM2 protein-protein interaction has been raised as a new cancer therapy in the medicinal community. In the current study, we report a successful application of an integrative protocol to design novel p53-derived peptides with cytotoxicity on human breast cancer cells. A quantitative structure-activity relationship-improved statistical potential was used to evaluate the binding potency of totally 24,054 single- and dual-point mutants of p53 peptide to MDM2 in a high-throughput manner, from which 46 peptide mutants with high predicted affinity and typical helical feature were involved in a rigorous modeling procedure that employed molecular dynamics simulations and post-binding energy analysis to systematically investigate the structural, energetic and dynamic aspects of peptide interactions with MDM2. Subsequently, a biological analysis was performed on a number of promising peptide candidates to determine their cytotoxic effects on human breast cancer cell line MDF-7. Six dual-point mutants were found to have moderate or high activities with their IC50 values ranging from 16.3 to 137.0 μM, which are better than that of wild-type p53 peptide (IC50 = 182.6 μM) and close to that of classical anticancer agent cis-platin (IC50 = 4.3 μM). Further, the most active peptide ETFSDWWKLLAE was selected as parent to further derive new mutants on the basis of the structural and energetic profile of its complex with MDM2. Consequently, three triple-point mutants (LTFSDWWKLLAE, ESFSDWWKLLAE and ETFADWWKLLAE) were obtained, and their biological activities (IC50 = 15.1, 27.0 and 8.7 μM, respectively) were determined to be comparable or better than the parent (IC50 = 16.3 μM).