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
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