Neuropeptide Y: Molecular Structure
Chemical properties, amino acid sequence, and structural analysis
📌TL;DR
- •Molecular formula: C190H287N55O57
- •Molecular weight: 4253.72 Da
- •Half-life: ~15-30 minutes (plasma)
Amino Acid Sequence
40 amino acids
Molecular Structure#
Neuropeptide Y (NPY) is a 36-amino acid peptide with a C-terminal amide. It adopts the characteristic PP-fold (pancreatic polypeptide fold) tertiary structure: an N-terminal polyproline helix (residues 1-8), a beta-turn (residues 9-14), and a long amphipathic alpha-helix (residues 15-36) that pack against each other through hydrophobic interactions.
Amino Acid Sequence#
| Property | Value |
|---|---|
| Sequence | YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY-NH2 |
| Length | 36 amino acids |
| Molecular weight | 4253.72 Da |
| Molecular formula | C190H287N55O57 |
| CAS number | 82785-45-3 |
| PDB ID | 1RON |
| Family | Pancreatic polypeptide family (NPY, PYY, PP) |
| C-terminus | Amidated (essential for bioactivity) |
Receptor Binding#
NPY interacts with five receptor subtypes (Y1-Y5), all G protein-coupled receptors that signal through Gi/Go:
| Receptor | Distribution | Primary Function |
|---|---|---|
| Y1 | Cortex, hippocampus, amygdala | Anxiolysis, anti-depression, vasoconstriction |
| Y2 | Hippocampus, hypothalamus | Presynaptic autoreceptor, memory |
| Y4 | Gut, brainstem | Feeding, GI function |
| Y5 | Hypothalamus | Appetite stimulation |
The C-terminal pentapeptide (residues 32-36) is critical for receptor binding, with the terminal Tyr-NH2 being absolutely required for biological activity.
Pharmacokinetic Properties#
| Parameter | Details |
|---|---|
| Half-life | ~15-30 minutes (plasma) |
| Route | Intranasal (clinical trials), IV/ICV (research) |
| BBB penetration | Poor (requires intranasal delivery for CNS access) |
| Metabolism | Dipeptidyl peptidase IV (DPP-IV) cleaves N-terminal residues |
| Key metabolite | NPY(3-36), which is Y2/Y5-selective |
NPY is rapidly degraded in plasma by dipeptidyl peptidase IV (DPP-IV), which cleaves the N-terminal Tyr-Pro to produce NPY(3-36). This metabolite loses Y1 affinity but retains Y2 and Y5 activity, functionally shifting the receptor selectivity profile.
Stability Characteristics#
NPY is relatively stable as a lyophilized powder stored at -20 degrees C. In solution, it is susceptible to enzymatic degradation. The PP-fold tertiary structure provides some resistance to general proteases, but the N-terminus is vulnerable to DPP-IV.
Molecular Context#
Neuropeptide Y belongs to the Neuropeptide category of research peptides. The molecular properties of Neuropeptide Y determine its pharmacological behavior, including receptor binding, distribution, metabolism, and elimination. Understanding these properties is fundamental to interpreting clinical data and designing research protocols.
Structural Overview#
Neuropeptide Y is characterized as: Neuropeptide Y is a 36-amino acid C-terminally amidated peptide with a characteristic PP-fold (pancreatic polypeptide fold) structure consisting of an N-terminal polyproline helix (residues 1-8) connected by a beta-turn (residues 9-14) to a long amphipathic alpha-helix (residues 15-36). The C-terminal amidated tyrosine is essential for receptor binding..
Amino Acid Sequence Details#
The amino acid sequence of Neuropeptide Y is: YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY-NH2. This sequence determines the peptide's three-dimensional structure, receptor binding properties, and biological activity.
Pharmacokinetic Profile#
Half-Life: ~15-30 minutes (plasma)
The half-life of a peptide influences dosing frequency, duration of effect, and the clinical utility of the compound. Researchers should consider the half-life when designing experimental protocols.
Related Reading#
Frequently Asked Questions About Neuropeptide Y
What type of peptide is Neuropeptide Y?
Neuropeptide Y (NPY) is a 36-amino acid endogenous peptide and one of the most abundant neuropeptides in the brain. It acts through Y1, Y2, Y4, and Y5 receptor subtypes to regulate appetite, anxiety, stress response, and circadian rhythms. Reduced NPY levels are associated with PTSD and depression. Intranasal NPY delivery has been tested in early clinical trials for major depression, showing preliminary evidence of antidepressant effects within 24-48 hours.
What is the half-life of Neuropeptide Y?
The reported half-life of Neuropeptide Y is ~15-30 minutes (plasma). Half-life can vary depending on the route of administration, formulation, and individual factors. This information is based on available preclinical or pharmacokinetic data.
What is the amino acid sequence of Neuropeptide Y?
The amino acid sequence of Neuropeptide Y is YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY-NH2. Neuropeptide Y is a 36-amino acid C-terminally amidated peptide with a characteristic PP-fold (pancreatic polypeptide fold) structure consisting of an N-terminal polyproline helix (residues 1-8) connected by a beta-turn (residues 9-14) to a long amphipathic alpha-helix (residues 15-36). The C-terminal amidated tyrosine is essential for receptor binding.. This sequence determines its biological activity and binding properties.
How stable is Neuropeptide Y in storage?
Neuropeptide Y is typically supplied as a lyophilized powder for maximum stability. Neuropeptide Y is a 36-amino acid C-terminally amidated peptide with a characteristic PP-fold (pancreatic polypeptide fold) structure consisting of an N-terminal polyproline helix (residues 1-8) connected by a beta-turn (residues 9-14) to a long amphipathic alpha-helix (residues 15-36). The C-terminal amidated tyrosine is essential for receptor binding.. When reconstituted, it should be stored refrigerated at 2-8 degrees C and protected from light. Lyophilized powder should be stored at -20 degrees C.
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