Blood-vessel-tightening peptide fragment (FLDIIW)
A lab-made six-amino-acid snippet based on the natural hormone endothelin-1, which tightens blood vessels. Used only as a research tool to study how small changes in the peptide's shape affect its activity.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
FLDIIW is a six-amino-acid research peptide built as an analog of the natural hormone endothelin-1. Endothelin-1 is a 21-residue peptide that the body uses to constrict blood vessels, and almost all of its activity comes from its last six residues — the C-terminal hexapeptide His-Leu-Asp-Ile-Ile-Trp (HLDIIW), spanning positions 16–21. FLDIIW is the variant in which position 16 has been switched from histidine (H) to phenylalanine (F); the remaining five residues are unchanged. It is not a drug. It is a single data point in a structure–activity series cataloged in ChEMBL (compound CHEMBL273391) and used to map which side chains at the C-terminus of endothelin matter for binding the endothelin A receptor.
History
The biological importance of the endothelin C-terminal hexapeptide was established at the end of the 1980s, when Maggi and colleagues (European Journal of Pharmacology, 1989) showed that the isolated fragment endothelin-(16–21) is enough to discriminate between endothelin receptor subtypes. That observation made the six residues HLDIIW a natural starting scaffold for designing small peptide antagonists. In the early 1990s, the Parke-Davis group around Doherty published systematic position-by-position scans of this hexapeptide — both an L-to-D scan that surfaced the D-His16 series (Doherty and colleagues, Bioorganic & Medicinal Chemistry Letters, 1993) and a broader side-chain replacement study (Doherty and colleagues, Journal of Medicinal Chemistry, 1993). FLDIIW belongs to that family of mono-substituted ET-(16–21) analogs: it tests what happens to endothelin-A receptor binding when the imidazole ring of His16 is replaced by the aromatic ring of phenylalanine.
What it does
In
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 18400 nM | GPCRDB/ChEMBL |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10319,
sequence = {FLDIIW},
target = {ednra},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}