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[D-Pro2,D-Phe7,D-Trp9]-Substance P is a full-length Substance P analog containing D-Pro2, D-Phe7 and D-Trp9 substitutions.
The peptide is pharmacologically notable because its behavior varies between biological preparations. It has been described as a Substance P antagonist in some systems but can also display agonist or partial agonist activity in others.
Product Information
| Product Name | [D-Pro2,D-Phe7,D-Trp9]-Substance P |
| Catalog No. | AS2363 |
| CAS No. | 77275-70-8 |
| Sequence | Arg-D-Pro-Lys-Pro-Gln-Gln-D-Phe-Phe-D-Trp-Leu-Met-NH2 |
| Peptide Length | 11 residues |
| Molecular Formula | C72H105N19O13S |
| Molecular Weight | Approximately 1476.8 Da |
| Key Modifications | D-Pro2; D-Phe7; D-Trp9 |
| C-Terminus | Amidated |
| Pharmacological Profile | Tissue-dependent partial agonist / antagonist |
Stereochemical Modification of the Substance P Pharmacophore
The molecule retains the side-chain identities of Pro2 and Phe7 while reversing their stereochemistry and replaces Gly9 with D-Trp. These changes substantially alter the three-dimensional presentation of the C-terminal receptor-interaction region.
Agonist and Antagonist Behavior Depends on the Assay
Early studies identified [D-Pro2,D-Phe7,D-Trp9]-Substance P as an antagonist in several peripheral preparations. Other experiments demonstrated clear agonist activity, including neuronal responses and vascular or smooth-muscle effects.
In rat colon muscularis mucosae, the analog produced a maximum response of approximately 30% of the Substance P maximum, consistent with partial agonist behavior in that preparation.
This is an important experimental distinction. We do not recommend labeling the peptide simply as a “selective Substance P antagonist” because intrinsic activity can become apparent depending on receptor population and tissue context.
Research Applications
[D-Pro2,D-Phe7,D-Trp9]-Substance P can support partial agonism research, tachykinin receptor pharmacology, Substance P antagonist studies and investigations of how D-amino-acid substitutions alter efficacy as well as affinity.
Frequently Asked Questions
Is this peptide an agonist or antagonist?
It can exhibit both behaviors depending on the biological preparation. Partial agonist activity has been demonstrated in some smooth-muscle systems.
Why is the assay system important?
A partial agonist may appear antagonistic when competing with a higher-efficacy agonist but can produce its own response when tested alone. Receptor population and coupling efficiency can therefore change the observed pharmacology.
Does the peptide retain Met11?
Yes. Native Met11 remains at the amidated C-terminus.