dbacp03182
General Description
Peptide name : H-12
Source/Organism : Synthetic construct
Linear/Cyclic : Linear
Chirality : L
Sequence Information
Sequence : IKLSKETKDNLKKVLKGAIKGAIAVAKMV
Peptide length: 29
C-terminal modification: Linear
N-terminal modification : Amidation
Non-natural peptide information: None
Activity Information
Assay type : MTT assay
Assay time : 48h
Activity : IC50 : 4.28 ± 0.38 μM
Cell line : HepG2
Cancer type : Not found
Other activity : Not found
Physicochemical Properties
Amino acid composition bar chart :
Molecular mass : 3095.8277 Dalton
Aliphatic index : 1.244
Instability index : -8.3793
Hydrophobicity (GRAVY) : 0.0897
Isoelectric point : 10.222
Charge (pH 7) : 5.756
Aromaticity : 0
Molar extinction coefficient (cysteine, cystine): (0, 0)
Hydrophobic/hydrophilic ratio : 1.23076923
hydrophobic moment : 0.1205
Missing amino acid : C,R,W,H,Q,P,F,Y
Most occurring amino acid : K
Most occurring amino acid frequency : 8
Least occurring amino acid : S
Least occurring amino acid frequency : 1
Structural Information
3D structure :
Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.1, 0.3)
SMILES Notation: CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O
Secondary Structure :
| Method | Prediction |
|---|---|
| GOR | HHHHHHHHHHHHHHHHHHHHHHHHHHHHH |
| Chou-Fasman (CF) | CHHHHHCHHHHHHCHHHHHHHEECCCCCC |
| Neural Network (NN) | HHCCCCCHHHHHHHHHHHHCHHHHHHHHH |
| Joint/Consensus | HHHHHHCHHHHHHHHHHHHHHHHHHHHHH |
Molecular Descriptors and ADMET Properties
Molecular Descriptors: Click here to download
ADMET Properties: Click here to download
Cross Referencing databases
CancerPPD : Not available
ApIAPDB : Not available
CancerPPD2 ID : Not available
Reference
1 : Li Y, et al. Improving Selectivity, Proteolytic Stability, and Antitumor Activity of Hymenochirin-1B: A Novel Glycosylated Staple Strategy. ACS Chem Biol. 2019; 14:516-525. doi: 10.1021/acschembio.9b00046
Literature
Paper title : Improving Selectivity, Proteolytic Stability, and Antitumor Activity of Hymenochirin-1B: A Novel Glycosylated Staple Strategy.
Doi : https://doi.org/10.1021/acschembio.9b00046
Abstract : As a host defense peptide, hymenochirin-1B has attracted increasing attention for its strong cytotoxic activities. However, its poor selectivity and proteolytic stability remain major obstacles for clinical application. To solve these problems, we designed and synthesized a series of peptide analogues of hymenochirin-1B based on cationic residue substitution and stapling combined with a glycosylation strategy. Some analogues showed improvement not only in selectivity and proteolytic stability but also in antitumor activity. Among them, the glycosylated stapled peptide H-58 was identified as the most potential antitumor peptide. Flow cytometry and a competitive binding assay revealed that H-58 displayed significant antitumor selectivity. Confocal microscopy and nuclear staining with Hoechst dye demonstrated that H-58 entered the nucleus and caused DNA damage. In summary, the strategy of glycosylated stapled peptides is a promising approach for improving the antitumor selectivity, proteolytic stability, and antitumor activity of hymenochirin-1B, which can be used for other bioactive peptide modifications.