DRAVP ID  DRAVPe02311

Peptide Name   4-Link

Sequence  YGRKKRRQRRRGSGIEPHDWTKCITOKIDQIIHDFVDK

Sequence Length  38

UniProt ID  No entry found

Taxon ID  None

Source  Synthetic construct

Validation   Experimentally Validated

Gene Name/ID  Not Available

GenBank  Not Available

Amino Acid position  Not Available

Domain Accession ID  Not Available

Nucleotide sequence ID  Not Available

Molecular Type  Not Available

Chromosomal Position  Not Available

Target Organism  EBOV

Assay  Not Available

Activity 

• [Ref:23962564]EBOV:IC50=40 microM

Hemolytic Activity  No hemolysis information or data found in the reference(s) presented in this entry

Cytotoxicity 

• [Ref:23962564]Non-toxic (At 40 microM concentration, peptide 4-Link demonstrated good tolerance by Vero cells, as evaluated through visual examination and a commercial viability assay. At the same con

Binding Target  Glycoprotein.

Mechanism  Peptide 4-Link demonstrated strong neutralization of vesicular stomatitis virus particles carrying the Ebola virus glycoprotein (VSV-GP), resulting in a notable decrease in infection at a concentration of 40 microM. Its effectiveness against Ebola virus was evaluated by measuring the reduction in infection events induced by VSV-GP in its presence. Additionally, 4-Link displayed inhibitory effects on VSV particles bearing their native glycoprotein G (VSV-G), a lesser extent than VSV-GP, suggesting a degree of specificity towards the Ebola virus glycoprotein. These findings suggest that 4-Link likely targets the viral entry process common to both viruses, with a higher affinity for the Ebola virus glycoprotein, thereby inhibiting infection.

PDB ID  None

Predicted Structure Download 

Linear/Cyclic  Linear

N-terminal Modification  Free

C-terminal Modification  Acetylation

Other Modification  In the peptide sequence, N-terminal acetylation (Ac-) blocks the free amine group, protecting the peptide from exopeptidase degradation and increasing stability. To promote an alpha-helical conformation, side chain-side chain cross-links were introduced, particularly between Cys (C) at position 23 and an Ornithine (O) residue replacing Lys (K), positioned for cross-linking (at i and i + 3). These modifications help stabilize the helical structure, especially in regions predisposed to alpha-helix

Stereochemistry  L

Literature 1

Title   C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking

Pubmed ID   23962564

Reference   Bioorg Med Chem Lett. 2013;23(19):5356-60.

Author   Higgins CD, Koellhoffer JF, Chandran K

DOI   10.1016/j.bmcl.2013.07.056