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[D-Pro2,D-Trp7,9]-Substance P is a full-length Substance P analog containing D-Pro2 and D-Trp substitutions at positions 7 and 9.
The peptide was among the early analogs developed to antagonize Substance P responses. Its pharmacology is strongly assay-dependent, making it particularly useful as a historical tachykinin SAR reagent rather than as a universally selective NK1 antagonist.
Product Information
| Product Name | [D-Pro2,D-Trp7,9]-Substance P |
| Catalog No. | AS2362 |
| CAS No. | 80434-86-2 |
| Sequence | Arg-D-Pro-Lys-Pro-Gln-Gln-D-Trp-Phe-D-Trp-Leu-Met-NH2 |
| Peptide Length | 11 residues |
| Molecular Formula | C74H106N20O13S |
| Molecular Weight | Approximately 1515.8 Da |
| Key Modifications | D-Pro2; D-Trp7; D-Trp9 |
| C-Terminus | Amidated |
| Pharmacological Profile | Assay-dependent Substance P antagonist analog |
Early Competitive Substance P Antagonist Design
D-Pro2 and D-Trp7,9 substitutions were introduced during early attempts to convert the native Substance P agonist into competitive peptide antagonists.
In several peripheral preparations, [D-Pro2,D-Trp7,9]-Substance P inhibited Substance P responses and was described as a competitive antagonist.
Why the Experimental Model Matters
Later studies demonstrated that the same classification does not apply uniformly across biological systems. In rat spinal cord and caudal trigeminal nucleus experiments, the peptide was not considered a specific antagonist suitable for identifying endogenous Substance P pathways.
Intrathecal studies also reported behavioral and motor effects that complicated interpretation of apparent antinociceptive activity.
We recommend using this analog with a receptor-selective control and reporting the tissue and species explicitly. This is especially important when comparing historical peptide antagonist data with modern recombinant NK1 receptor assays.
Research Applications
The peptide can support Substance P antagonist research, historical tachykinin pharmacology, D-amino-acid SAR and studies of assay-dependent agonist–antagonist behavior.
Frequently Asked Questions
Is [D-Pro2,D-Trp7,9]-Substance P a selective NK1 antagonist?
It has antagonist activity in several preparations, but its specificity is strongly model-dependent. It should not be presented as a universally selective NK1 antagonist.
Why is this distinction important?
Some CNS studies found effects inconsistent with simple specific Substance P antagonism, so biological responses require appropriate controls.
How many D-amino acids are present?
Three: D-Pro2, D-Trp7 and D-Trp9.