[(4Cl)DPhe6,Leu17] VIP

[4Cl-D-Phe6,Leu17]-VIP is a selective antagonist analog of vasoactive intestinal peptide (VIP) designed to competitively block VIP receptor signaling while retaining high-affinity receptor binding. The compound introduces two key substitutions into the native 28-residue VIP sequence: (1) D-phenylalanine with a para-chloro substituent (4-Cl-D-Phe) at position 6, which disrupts the turn structure required for receptor activation while preserving binding affinity by providing a bulky para-substituted aromatic at a contact position; and (2) leucine in place of the native methionine at position 17, which alters the helical hydrophobic face used for receptor coupling.

Together these modifications create a compound with VIP-receptor affinity but without the adenylate cyclase activation (cAMP generation) that defines native VIP's biological signal — a classical competitive antagonist profile at VPAC1 and VPAC2 receptors. Related VIP antagonist scaffolds have been applied to study the physiological contributions of VIP receptor signaling in smooth muscle, secretomotor neurons, and immune-cell contexts.

Potential Research Applications: VPAC1/VPAC2 receptor pharmacology and competitive antagonism studies — defining the contribution of endogenous VIP to cAMP-dependent pathways in isolated tissue or cell-based assays Non-adrenergic, non-cholinergic (NANC) neurotransmission research in gut smooth muscle and enteric secretomotor neurons Neuroimmune VIP signaling studies (T cell, dendritic cell, macrophage VPAC receptor expression) Control reagent for dissecting VIP vs. PACAP contributions in dual VIP/PACAP receptor preparations

What the Original Pharmacology Actually Showed

The compound was designed from structure-activity work on rat growth hormone-releasing factor at the VIP receptor of exocrine pancreas. In that 1986 characterization, micromolar concentrations of synthetic [4Cl-D-Phe6,Leu17]VIP competitively antagonized VIP-stimulated amylase release in pancreatic preparations and VIP-stimulated short-circuit current in a colonic tumor cell line, while leaving secretin, GRF, and glucagon receptor agonists unaffected. That receptor selectivity is the reason the peptide is still used as a reference antagonist rather than a broad class-B GPCR blocker.

Two later in vivo studies define its practical limits. In urethane-anesthetized rats, intravenous infusion blocked the gastric mucosal hyperemia and hypotension produced by close-intra-arterial VIP without changing basal blood flow or pressure. In the awake dog, intracoronary infusion produced only modest inhibition of VIP-induced coronary vasodilation and no change in resting coronary resistance, heart rate, or contractility. Researchers should therefore expect clean antagonism of exogenous VIP but should not assume the antagonist will unmask a large tonic VIP contribution in every vascular bed.

Live Market Data on Peptides.SO (listing data on file as of 13 September 2026)

Peptides.SO currently tracks 1 listing for [4Cl-D-Phe6,Leu17]-VIP, from CPC Scientific at $104.50 (priced per mg on the listing). For scale, the median list price across the 1,432 priced listings in the platform's research-peptides category is $82.50, so this antagonist sits roughly 27% above the category midpoint, which is consistent with a 28-residue custom sequence carrying a non-natural chlorinated D-amino acid. No supplier on the platform currently has a testing score or a certificate-of-analysis link on file for any product, so purity claims for this reagent should be confirmed directly with the vendor's lot-specific HPLC and mass-spectrometry data before use. See the live supplier table on this page for the current price.

Frequently Asked Questions

Is [4Cl-D-Phe6,Leu17]-VIP selective for VPAC1 or VPAC2? The founding study characterized it against the VIP receptor of exocrine pancreas and a colonic cell line, before the VPAC1/VPAC2/PAC1 nomenclature existed. It is generally treated as a non-subtype-selective VIP receptor antagonist; researchers who need subtype resolution should confirm activity in cells expressing a single cloned receptor.

What concentration range has been reported in vitro? The original pancreatic and colonic assays used micromolar concentrations to achieve competitive antagonism. A full dose-response against a fixed VIP concentration is advisable in any new preparation.

How does it compare to VIP(10-28) or PACAP(6-38)? Those are truncated-sequence antagonists; [4Cl-D-Phe6,Leu17]-VIP is a full-length substituted analog. The full-length scaffold tends to retain binding affinity better, at the cost of some residual partial-agonist activity in some systems, so a vehicle-only and agonist-only control arm is essential.

Related Pages on Peptides.SO

Native peptide and receptor background: VIP (vasoactive intestinal peptide) price comparison and the VIP research profile. For the sister ligand at the same receptor family, see the PACAP research overview. Use the reconstitution calculator to convert vial mass to molar stock concentration, and the CoA interpretation guide when evaluating vendor purity documents.

Cited Research

Pandol SJ et al.. Vasoactive intestinal peptide receptor antagonist [4Cl-D-Phe6, Leu17] VIP. Am J Physiol. 1986. PubMed 2421587

Király A et al.. Influence of [4Cl-D-Phe6,Leu17]VIP on VIP- and central TRH-induced gastric hyperemia. Peptides. 1997. PubMed 9392832

Quebbemann BB et al.. Effects of intracoronary infusion of the vasoactive intestinal peptide antagonist [4Cl-D-Phe6-Leu17]VIP in the awake dog. Peptides. 1991. PubMed 1800959

Harmar AJ et al.. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012. PubMed 22289055

For laboratory research use only. Not for human or veterinary use, diagnosis, treatment, cure, or prevention of any disease. THIS PRODUCT IS NOT FOR HUMAN CONSUMPTION.