dbacp07870
General Description
Peptide name : R-Lycosin I derivative 8a
Source/Organism : Monosaccharide Analogue of Anticancer Peptide R-Lycosin-I
Linear/Cyclic : Linear
Chirality : L
Sequence Information
Sequence : RGWFRAMRSIARFIARERLRGHL
Peptide length: 23
C-terminal modification: Linear
N-terminal modification : Free
Non-natural peptide information:
Activity Information
Assay type : CCK-8 assay
Assay time : 24-h
Activity : IC50 = 6.9 ± 0.4 µM
Cell line : PC-3
Cancer type : Prostate Cancer
Other activity : Anticancer
Physicochemical Properties
Amino acid composition bar chart :
Molecular mass : 2856.366 Dalton
Aliphatic index : 0.808
Instability index : 31.7478
Hydrophobicity (GRAVY) : -0.487
Isoelectric point : 12
Charge (pH 7) : 5.85
Aromaticity : 13.04
Molar extinction coefficient (cysteine, cystine): (0, 0)
Hydrophobic/hydrophilic ratio : 1.3
hydrophobic moment : -0.701
Missing amino acid : C,D,K,N,P,Q,T,V,Y
Most occurring amino acid : R
Most occurring amino acid frequency : 7
Least occurring amino acid : W
Least occurring amino acid frequency : 1
Structural Information
3D structure :
Secondary structure fraction (Helix, Turn, Sheet): (30., 13., 30.)
SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CC(C)C)C(=O)O
Secondary Structure :
| Method | Prediction |
|---|---|
| GOR | THHHHHHHHHHHHHHHHHHTTTE |
| Chou-Fasman (CF) | EEHHHHEEEEEEEHHHHCCCCCC |
| Neural Network (NN) | CCCHHHHHHHHHHHHHHHHHHCC |
| Joint/Consensus | CCHHHHHHHHHHHHHHHHHCCCC |
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: 6255
Reference
1 : Zhang P, et al. Monosaccharide Analogues of Anticancer Peptide R-Lycosin-I: Role of Monosaccharide Conjugation in Complexation and the Potential of Lung Cancer Targeting and Therapy. J Med Chem. 2019; 62:7857-7873. doi: 10.1021/acs.jmedchem.9b00634
Literature
Paper title : Monosaccharide Analogues of Anticancer Peptide R-Lycosin-I: Role of Monosaccharide Conjugation in Complexation and the Potential of Lung Cancer Targeting and Therapy.
Doi : https://doi.org/10.1021/acs.jmedchem.9b00634
Abstract : Glycoconjugation is a promising modification strategy for the optimization of peptide drugs. In this study, five different monosaccharide derivatives (7a-e) were covalently linked to the N-terminal of R-lycosin-I, which yielded five glycopeptides (8a-e). They demonstrated increased or reduced cytotoxicity depending on monosaccharide types, which might be explained by the changes of physicochemical properties. Among all synthesized glycopeptides, only 8a exhibited increased cytotoxicity (IC<sub>50</sub> = 9.6 ± 0.3 μM) and selectivity (IC<sub>50</sub> = 37.4 ± 5.9 μM). The glucose transporter 1 (GLUT1) with high expression in cancer cells was approved to be involved in the cytotoxicity and selectivity enhancement of 8a. Furthermore, 8a but not R-lycosin-I inhibited tumor growth in the nude mice xenograft model without generating side effects intraperitoneally. Taken together, this study reveals the different monosaccharide roles in peptide modification and also provides an optimized anticancer peptide with high activity and selectivity, that is, 8a might be a promising lead for developing anticancer drugs.