[Trp7,β-Ala8]-Neurokinin A (4-10), also known as R-486 or MEN 10295, is a synthetic heptapeptide analog of Neurokinin A (4-10) used in tachykinin receptor pharmacology.

The peptide has the sequence Asp-Ser-Phe-Trp-β-Ala-Leu-Met-NH₂. Compared with native Neurokinin A (4-10), Val7 is replaced by tryptophan and Gly8 is replaced by β-alanine. This combination produces a pharmacological profile associated with NK3 receptor antagonism.

Product Information

Trp7 and β-Ala8 Substitutions in the NKA(4-10) Scaffold

Native Neurokinin A (4-10) contains the sequence Asp-Ser-Phe-Val-Gly-Leu-Met-NH₂. R-486 preserves the overall C-terminal NKA scaffold while introducing two coordinated substitutions: Val7 → Trp and Gly8 → β-Ala.

Trp introduces a larger aromatic side chain at position 7, while β-Ala adds an additional methylene group to the peptide backbone at position 8. The resulting change is therefore more substantial than a simple conservative side-chain replacement.

These two modifications are particularly useful in structure–activity studies because the closely related [β-Ala8]-Neurokinin A (4-10), which retains Val7, is a well-established NK2-selective agonist. Addition of the Trp7 substitution produces a markedly different pharmacological profile.

NK3 Receptor Antagonism

R-486 was developed during early studies of tachykinin receptor subtype pharmacology and has been used as a peptide antagonist in NK3 receptor preparations.

In the rat portal vein, a classical NK3 receptor bioassay, R-486 showed antagonist activity with a reported pA₂ of approximately 7.45. Its apparent activity differed in other tissue preparations, illustrating the strong assay and species dependence of historical tachykinin pharmacology.

We recommend using historical pA₂ values as comparative pharmacological data rather than treating them as universal affinity constants. Studies using recombinant human TACR3 should establish potency directly under the selected binding or functional assay conditions.

Why Compare R-486 with [β-Ala8]-NKA(4-10)?

The two peptides differ primarily at position 7 while sharing the β-Ala8 backbone modification. This makes them useful as a paired comparison for determining how an aromatic Trp substitution changes receptor recognition within an NKA-derived scaffold.

For receptor subtype or SAR experiments, using both analogs can provide more information than testing either peptide alone because it separates the contribution of β-Ala8 from the additional Val7 → Trp substitution.

Research Applications

[Trp7,β-Ala8]-Neurokinin A (4-10) can be used in tachykinin receptor pharmacology, NK3 antagonist studies, Neurokinin A structure–activity research, receptor subtype comparison and functional studies involving NK1, NK2 and NK3 receptor systems.

The peptide also retains a C-terminal methionine. For experiments sensitive to peptide integrity, methionine oxidation should be considered during storage and sample handling because oxidation produces a +16 Da mass shift that can be detected by mass spectrometry.

Related tachykinin analogs, non-natural amino acid substitutions and project-specific purity specifications can also be produced through our Chemical Peptide Synthesis service.

Frequently Asked Questions

What are R-486 and MEN 10295?

R-486 and MEN 10295 are alternative names for [Trp7,β-Ala8]-Neurokinin A (4-10), CAS 132041-95-3.

Is R-486 an NK2 agonist?

R-486 is primarily used as a peptide NK3 receptor antagonist. It should not be confused with [β-Ala8]-Neurokinin A (4-10), which retains Val7 and is widely used as an NK2-selective agonist.

How does R-486 differ from [β-Ala8]-Neurokinin A (4-10)?

Both contain β-Ala at position 8, but R-486 additionally replaces Val7 with Trp. This additional aromatic substitution substantially changes the pharmacological behavior of the peptide.

Is the C-terminus amidated?

Yes. The peptide terminates in Met-NH₂, preserving the amidated C-terminal feature found in the NKA fragment.

Can the published pA2 value be used for human NK3 receptors?

Not directly. The commonly cited value was obtained in an isolated rat tissue assay. Recombinant human TACR3 studies may produce different apparent affinity or potency values depending on receptor expression, assay format and signaling readout.

Research Use Only.