DRAVP ID  DRAVPe02265

Peptide Name   Mirabamide A

Sequence  XXXAGXXXKTGX

Sequence Length  5

UniProt ID  No entry found

Taxon ID  None

Source  marine sponge Siliquariaspongia mirabilis

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  HIV-1

Assay  disk diffusion assays.

Activity 

• [Ref: 17963357] Mirabamide A inhibited HIV-1 in neutralization and fusion assays with IC50 values between 40 and 140 nM

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

Cytotoxicity  No cytotoxicity information found in the reference(s) presented

Binding Target  Glycoprotein.

Mechanism  The mechanism of action for peptides E through H likely involves their amphipathic and cyclic nature, which enables them to interact with both viral and host cell components to inhibit HIV-1 infection. These peptides may target the HIV-1 envelope glycoproteins, such as gp120 and gp41, which are critical for viral entry into host cells. By binding to gp120, they could block its interaction with the CD4 receptor or CCR5/CXCR4 co-receptors, preventing viral attachment. Additionally, interference with gp41 could disrupt the membrane fusion process required for viral entry. Their structural properties also suggest potential interactions with the host cell membrane, altering its lipid microdomains and impeding the fusion process. Furthermore, these peptides might inhibit the HIV-1 reverse transcriptase enzyme, blocking viral RNA to DNA transcription, or interact with viral assembly proteins to disrupt the formation of infectious virions. The exact mechanism for each peptide requires further investigation, including binding studies and structural analyses, to elucidate their precise targets and pathways of action.

PDB ID  None

Predicted Structure Download 

Linear/Cyclic  Cyclic

N-terminal Modification  The N-terminal contains 4-chloro-L-homoproline (ClHPr) in A and L-homoproline (HPr) in B (without chlorine).

C-terminal Modification  The C-terminal is closed via an ester bond to form a macrocyclic structure. This esterification involves a β-hydroxyl group, making the C-terminal non-free for every variant.

Other Modification  Cl at terminal proline.Contains ?-methoxytyrosine glycosylated with 4′-o-?-l-rhamnopyranoside.This sequence contains several modified residues. X at position 1 is 4-chlorohydroxyproline (ClHPr), X at position 2 is β-O-methyltyrosine (β-OMeTyr), X at position 3 is N-methylthreonine (NMeThr), X at position 6 is 3-O-methylalanine (3-OMeAla), X at position 7 is 3-hydroxyleucine (3-OHLeu), X at position 8 is 3,4-dimethylglutamine (3,4-DiMeGln), X at position 9 is diaminobutyric acid (Dab), and X at p

Stereochemistry  L

Literature 1

Title   Chemical Reactivity Properties, pKa Values, AGEs Inhibitor Abilities and Bioactivity Scores of the Mirabamides A–H Peptides of Marine Origin Studied by Means of Conceptual DFT;

Pubmed ID    30154377;

Reference   Mar Drugs. 2018 Aug 28;16(9):302;

Author   Frau J, Flores-Holguín N, Glossman-Mitnik D:

DOI   10.3390/md16090302;

Literature 2

Title   Mirabamides A-D, depsipeptides from the sponge Siliquariaspongia mirabilis that inhibit HIV-1 fusion

Pubmed ID   17963357

Reference   Journal of natural products, 70(11), 1753–1760.

Author   Plaza, A., Gustchina, E., Baker, H. L., Kelly, M., & Bewley, C. A. (2007).

DOI   10.1021/np070306k