[D-Trp2,7,9]-Substance P is a full-length Substance P analog containing D-tryptophan substitutions at positions 2, 7 and 9.

The extensive stereochemical modification changes the receptor-interaction profile of the native agonist and produces a peptide with tachykinin antagonist activity across multiple neurokinin receptor subtypes.

Product Information

Multiple D-Trp Substitutions

Changing residues to D-configuration alters the three-dimensional presentation of their side chains without simply changing elemental composition. The introduction of three D-Trp residues therefore produces a major stereochemical change relative to native Substance P.

D-amino-acid substitution can also alter recognition by peptide-degrading enzymes, although proteolytic resistance should be evaluated for the complete sequence rather than inferred from the presence of individual D-residues.

Activity Across Neurokinin Receptor Subtypes

Reported receptor data describe [D-Trp2,7,9]-Substance P as a broad tachykinin antagonist, with K_i values of approximately 1 μM at NK1, 1.3 μM at NK2 and about 9 μM at NK3.

This profile differs from highly selective modern small-molecule neurokinin antagonists. We consider the peptide most useful in historical tachykinin pharmacology and comparative peptide SAR rather than as a subtype-selective inhibitor.

Research Applications

The peptide can support tachykinin antagonist studies, D-amino-acid SAR, neurokinin receptor comparison and investigation of how peptide stereochemistry influences receptor activity.

Frequently Asked Questions

Is [D-Trp2,7,9]-Substance P selective for NK1?

No. Reported data indicate antagonist activity at NK1, NK2 and NK3 receptors, with the greatest affinity among these measurements at NK1 and NK2.

How many D-amino acids are present?

Three D-tryptophan residues are present at positions 2, 7 and 9.

Is the native Met11 retained?

Yes. The peptide still terminates in Leu-Met-NH₂.

Research Use Only.