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AOD-9604
Technical Peptide Reference | Orion Peptides Learning Library
AOD-9604 is a synthetic peptide composed of 16 amino acid residues. Its structure is derived from the C-terminal region of growth hormone, with an additional tyrosine residue at the N-terminus.
Unlike full-length growth hormone, which consists of 191 amino acids, AOD-9604 represents a short, chemically defined fragment analog.
One of its most distinctive structural features is an intramolecular disulfide bond between two cysteine residues. This bond creates a constrained loop within the peptide chain.
The resulting molecule combines a linear peptide backbone with an internally bridged region.
AOD-9604 is identified by CAS number 221231-10-3 and the molecular formula C₇₈H₁₂₃N₂₃O₂₃S₂.
Its relatively compact structure makes it a useful subject for studying peptide-fragment chemistry, disulfide-bond formation, conformational constraints, and analytical identification.
This reference explains the amino acid arrangement of AOD-9604, its relationship to the parent protein, structural characteristics, receptor-related laboratory findings, and methods used to characterize the compound.
AOD-9604 Molecular Reference
| Property | Scientific information |
|---|---|
| Compound name | AOD-9604 |
| Alternative name | AOD9604 |
| Structural designation | Tyr-hGH(177–191) |
| CAS number | 221231-10-3 |
| PubChem CID | 71300630 |
| Molecular formula | C₇₈H₁₂₃N₂₃O₂₃S₂ |
| Molecular weight | Approximately 1,815.1 g/mol |
| Amino acid count | 16 residues |
| Molecular classification | Synthetic growth-hormone fragment analog |
| Peptide structure | Linear backbone with an intramolecular disulfide bridge |
| Disulfide linkage | Cys7–Cys14 |
| N-terminal residue | Tyrosine |
| C-terminal residue | Phenylalanine |
| C-terminal group | Free carboxylic acid |
| Parent protein | Growth hormone |
| Principal analytical considerations | Peptide identity, disulfide integrity, chromatographic purity, molecular mass |
These identifiers apply to the disulfide-bridged free peptide. Acetate or other counterion-containing materials must be characterized according to their actual chemical composition.
1. Understanding AOD-9604 as a Protein Fragment Analog
AOD-9604 was developed from a defined region near the end of the growth hormone protein.
Proteins are composed of amino acid residues arranged in specific sequences.
Some protein regions contain structural elements that can be investigated separately from the complete molecule.
Researchers use synthetic fragments to understand how different parts of proteins contribute to molecular properties and interactions.
The Parent Growth Hormone Structure
Mature growth hormone consists of 191 amino acid residues.
Its folded structure contains several alpha-helical regions and two intramolecular disulfide bonds.
Disulfide bonds help stabilize parts of the protein’s three-dimensional structure.
One of these connections occurs near the C-terminal region.
AOD-9604 preserves the corresponding cysteine-linked structural element within a much shorter peptide.
What Does the Name Tyr-hGH(177–191) Mean?
The designation identifies the molecular origin of AOD-9604.
Tyr refers to the additional tyrosine residue.
hGH refers to the parent growth hormone sequence.
177–191 identifies the 15-residue segment of the parent protein.
The resulting synthetic molecule contains 16 residues: the additional tyrosine followed by the sequence corresponding to positions 177 through 191.
Is AOD-9604 Identical to hGH Fragment 176–191?
Not exactly.
The native 16-residue segment beginning at position 176 contains phenylalanine at its first position.
AOD-9604 instead contains an N-terminal tyrosine followed by the final 15 residues.
The names are sometimes used interchangeably in peptide catalogs, but the structures should be distinguished in technical documentation.
A precise compound reference should identify the actual sequence rather than relying only on a fragment number.
2. The Amino Acid Sequence of AOD-9604
The one-letter amino acid sequence is:
YLRIVQCRSVEGSCGF
The corresponding three-letter sequence is:
Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe
The peptide contains 16 residues.
Two cysteine residues form an intramolecular disulfide linkage.
Residue-by-Residue Sequence
| Position | Amino acid | Abbreviation |
|---|---|---|
| 1 | Tyrosine | Tyr (Y) |
| 2 | Leucine | Leu (L) |
| 3 | Arginine | Arg (R) |
| 4 | Isoleucine | Ile (I) |
| 5 | Valine | Val (V) |
| 6 | Glutamine | Gln (Q) |
| 7 | Cysteine | Cys (C) |
| 8 | Arginine | Arg (R) |
| 9 | Serine | Ser (S) |
| 10 | Valine | Val (V) |
| 11 | Glutamic acid | Glu (E) |
| 12 | Glycine | Gly (G) |
| 13 | Serine | Ser (S) |
| 14 | Cysteine | Cys (C) |
| 15 | Glycine | Gly (G) |
| 16 | Phenylalanine | Phe (F) |
Which Residues Are Chemically Important?
Several residues influence the peptide’s chemical behavior.
Tyrosine contains an aromatic group with ultraviolet absorbance properties.
Arginine contains a basic guanidinium group that can carry a positive charge.
Glutamic acid contains an acidic side chain.
Cysteine contains a sulfur-bearing group capable of forming disulfide bonds.
Leucine, isoleucine, valine, and phenylalanine contribute relatively hydrophobic side-chain characteristics.
The complete combination influences the peptide’s charge, solubility, chromatographic retention, and interactions with its environment.
3. The Disulfide Bridge: AOD-9604’s Defining Structural Feature
The intramolecular disulfide bond is particularly important for understanding AOD-9604.
This covalent linkage connects cysteine residues at positions 7 and 14.
A disulfide bond forms when the sulfur-containing thiol groups of two cysteine residues are oxidized and joined.
The resulting linkage is represented as:
Cys7–S–S–Cys14
Why Is This Bond Important?
A linear peptide chain can adopt many different conformations.
An intramolecular disulfide bond restricts some of that flexibility.
In AOD-9604, the connection creates a loop spanning residues 7 through 14.
This changes the molecular geometry compared with an otherwise identical peptide containing two unconnected cysteine thiols.
Is AOD-9604 a Cyclic Peptide?
AOD-9604 contains a cyclic region, but its complete backbone is not head-to-tail cyclized.
The two terminal ends remain separate.
It is therefore more precise to describe the molecule as a disulfide-bridged peptide rather than a fully backbone-cyclic peptide.
Reduced vs Oxidized Peptide
The two cysteine residues can be considered in different chemical states.
In the reduced form, each cysteine has a free thiol group.
In the oxidized, bridged form, the cysteines are connected by a disulfide bond.
The formation of one disulfide bond removes two hydrogen atoms from the reduced structure.
As a result, the reduced and oxidized forms have different molecular masses.
This distinction matters when interpreting mass spectrometry.
Why Does Disulfide Integrity Matter?
A disrupted disulfide bridge changes the peptide’s covalent structure.
The molecule may also adopt different conformations.
Therefore, analytical characterization may need to establish not only molecular mass but also the expected disulfide connectivity.
4. The N-Terminal Tyrosine Modification
AOD-9604 contains tyrosine at its N-terminus.
This residue distinguishes the synthetic sequence from the corresponding unmodified C-terminal segment.
What Makes Tyrosine Different from Phenylalanine?
Tyrosine and phenylalanine both contain aromatic rings.
However, tyrosine contains a hydroxyl group attached to its aromatic ring.
This introduces an additional oxygen atom and changes the residue’s chemical characteristics.
How Does Tyrosine Influence Analytical Detection?
Tyrosine absorbs ultraviolet light.
This property can contribute to ultraviolet-based peptide detection.
However, UV measurements require appropriate calibration and consideration of other absorbing groups.
The presence of tyrosine alone does not establish peptide identity or purity.
Why Does the Modification Affect Molecular Mass?
AOD-9604’s N-terminal tyrosine is part of its defined chemical structure.
Replacing phenylalanine with tyrosine in an otherwise corresponding fragment changes the elemental composition by one oxygen atom.
This produces a mass difference of approximately 16 Da.
That difference can help distinguish the structures during appropriately designed mass spectrometric analysis.
5. AOD-9604 and Growth Hormone Receptor Research
AOD-9604 is derived from a growth hormone sequence, but this does not mean it has the same receptor interactions as the complete hormone.
A full-length protein and a short peptide fragment can have very different structural and pharmacological properties.
Does AOD-9604 Bind the Growth Hormone Receptor?
An early published study examined AOD-9604 in a cell system expressing the growth hormone receptor.
The investigators reported that AOD-9604 did not compete with growth hormone for receptor binding under the conditions tested.
They also did not observe growth-hormone-receptor-mediated cell proliferation in that experimental system.
These findings support an important distinction between AOD-9604 and the intact parent hormone.
However, they do not establish a complete molecular mechanism for AOD-9604.
Is There a Confirmed AOD-9604 Receptor?
No single primary molecular receptor has been conclusively established for AOD-9604.
Several early preclinical studies investigated pathways associated with its experimental activity.
Those findings should not be represented as proof of direct binding to a specific receptor without appropriate binding and functional evidence.
Why Is This Relevant to Technical Research?
Researchers must distinguish between three different types of findings:
| Experimental observation | What it demonstrates |
|---|---|
| Molecular binding | Evidence of association with a target |
| Functional signaling response | Evidence of measurable activity in an assay |
| Downstream biological change | An observed effect that may involve several pathways |
A downstream response does not necessarily identify the direct molecular target.
This distinction is particularly important when discussing peptide fragments with incompletely characterized receptor pharmacology.
6. Physicochemical Characteristics of AOD-9604
AOD-9604 contains amino acids with different chemical properties.
These features influence its behavior in an experimental environment.
Polar and Charged Residues
Arginine contains a positively charged side chain under many aqueous conditions.
Glutamic acid contains an ionizable acidic group.
The N-terminal amino and C-terminal carboxyl groups also contribute to the peptide’s acid-base behavior.
The resulting net charge depends on solution pH.
Hydrophobic Residues
Leucine, isoleucine, valine, and phenylalanine contribute hydrophobic characteristics.
These groups can influence interactions with chromatographic stationary phases, surfaces, and other molecules.
Solubility
Peptide solubility depends on the exact material and experimental conditions.
Relevant variables include pH, ionic strength, concentration, counterion composition, and temperature.
A universal solubility value should not be presented without defining the conditions under which it was measured.
Aggregation and Surface Interactions
Peptide molecules may associate with each other or interact with laboratory surfaces.
Such behavior can influence analytical recovery and measured concentration.
The presence of a disulfide bridge may affect conformation, but it does not eliminate the possibility of aggregation or adsorption.
7. How Is AOD-9604 Analyzed in the Laboratory?
AOD-9604 requires analytical methods capable of examining its molecular identity, purity, and disulfide-containing structure.
Different techniques provide different types of information.
Mass Spectrometry
Mass spectrometry measures the mass-to-charge ratios of ions.
For AOD-9604, the expected mass should be calculated using the defined disulfide-bridged structure.
The observed result can then be compared with the reference mass.
However, an intact molecular mass alone cannot always establish the exact location of disulfide connectivity.
Reversed-Phase HPLC
Reversed-phase high-performance liquid chromatography separates components according to their interactions with the stationary and mobile phases.
It is commonly used to examine peptide-related impurities and chromatographic purity.
AOD-9604 contains polar, charged, and hydrophobic residues that contribute to its chromatographic behavior.
LC-MS Analysis
Liquid chromatography-mass spectrometry combines component separation with mass analysis.
This can help distinguish the main peptide from certain impurities or degradation compounds.
Disulfide Characterization
Where disulfide integrity is an important analytical requirement, suitable structural methods may be needed.
These can include appropriately validated mass spectrometric approaches designed to investigate disulfide connectivity.
The choice of method depends on the exact analytical question.
Analytical Techniques at a Glance
| Method | Primary research purpose |
|---|---|
| RP-HPLC | Chromatographic separation and purity |
| Mass spectrometry | Molecular mass-related identification |
| LC-MS | Characterization of separated molecular species |
| LC-MS/MS | Additional structural and fragmentation evidence |
| Disulfide-specific characterization | Assessment of cysteine connectivity |
| Quantitative peptide assay | Measurement of peptide content |
| Stability-indicating analysis | Detection of chemical changes over time |
No single analytical method establishes every relevant property.
8. What Does a Certificate of Analysis Establish?
A Certificate of Analysis, commonly called a COA, documents analytical testing performed on a particular batch or sample.
For AOD-9604, a detailed report may include the following information.
| COA information | Technical significance |
|---|---|
| Compound name | Identifies the reported research material |
| CAS number | Connects the material to its chemical reference |
| Lot number | Provides batch traceability |
| Expected molecular mass | Supports interpretation of MS data |
| Mass spectrometry result | Provides mass-related identity evidence |
| HPLC chromatogram | Displays chromatographic separation |
| HPLC purity | Reports chromatographic purity under the method used |
| Peptide assay | Reports content when separately tested |
| Water content | Provides moisture information if measured |
| Analytical date | Documents testing time |
| Laboratory identification | Identifies the testing organization |
Does 99% HPLC Purity Mean 99% Peptide Content?
No.
HPLC purity commonly describes the relative area of chromatographic peaks under a particular method.
Peptide content is a separate quantitative measurement.
Water, counterions, and substances not detected by the chromatographic method can influence the total composition of a sample.
Can a COA Confirm the Disulfide Bridge?
Only if the analytical methods provide suitable evidence.
A matching molecular mass supports the expected oxidized structure.
However, confirming the correct disulfide connectivity may require additional structural analysis.
Why Does the Exact Chemical Form Matter?
AOD-9604 free peptide and AOD-9604 acetate are not identical material descriptions.
Acetate counterions can affect the overall composition of a physical sample.
Analytical reports should therefore state the relevant chemical form when it is known.
9. Chemical Stability and Disulfide-Related Changes
The stability of a peptide is determined by its chemical structure and surrounding conditions.
AOD-9604 contains peptide bonds, charged functional groups, and a disulfide linkage.
Each can introduce specific analytical considerations.
Disulfide Reduction
Under reducing conditions, a disulfide bond may be converted into two free thiol groups.
This changes the covalent structure of the peptide.
Analytical results for the reduced and oxidized forms will differ.
Disulfide Exchange
Under certain chemical conditions, disulfide-containing compounds can undergo exchange reactions.
These may produce alternative molecular arrangements.
The occurrence and importance of such reactions depend on the sample composition and experimental environment.
Oxidation
Oxidative reactions may alter susceptible molecular groups.
For disulfide-containing peptides, sulfur chemistry is an important consideration during degradation studies.
Hydrolysis
Peptide bonds and certain side-chain groups may undergo hydrolytic reactions under appropriate conditions.
The rate depends on factors including pH, temperature, and exposure duration.
Physical Instability
Physical changes such as aggregation and adsorption can occur without necessarily changing the primary amino acid sequence.
Therefore, visual appearance alone is not sufficient for a complete stability evaluation.
Lyophilized and Solution-State Stability
Lyophilization can improve the storage characteristics of certain peptide formulations.
However, it does not guarantee a specific shelf life.
Solution-state materials may have different stability behavior.
Storage claims should be based on validated data for the exact material and formulation.
10. How AOD-9604 Differs from Other Growth Hormone-Related Peptides
Several peptides are discussed within growth hormone-related research, but they do not all share the same molecular structure or receptor mechanism.
AOD-9604 vs Sermorelin
Sermorelin is a 29-residue peptide derived from the N-terminal region of growth hormone-releasing hormone (GHRH).
AOD-9604 is a 16-residue fragment analog derived from the C-terminal region of growth hormone itself.
These are different parent proteins and different molecular structures.
Sermorelin acts through the GHRH receptor.
AOD-9604 does not have a comparably established primary receptor target.
AOD-9604 vs Tesamorelin
Tesamorelin is a modified 44-residue GHRH analog.
It contains an N-terminal chemical modification and acts through GHRH receptors.
AOD-9604 is a much shorter, disulfide-bridged fragment analog of growth hormone.
The two compounds should not be classified as equivalent GHRH agonists.
Molecular Comparison
| Feature | AOD-9604 | Sermorelin | Tesamorelin |
|---|---|---|---|
| Peptide residues | 16 | 29 | 44 |
| Parent sequence | Growth hormone C-terminal region | GHRH N-terminal region | Modified GHRH |
| Structural feature | Disulfide bridge | Amidated linear peptide | N-terminal modification |
| Primary receptor | Not definitively established | GHRHR | GHRHR |
| Growth hormone fragment | Yes | No | No |
| GHRH analog | No | Yes | Yes |
These differences illustrate why peptide classification should be based on chemical structure rather than broad similarities in naming.
11. Frequently Asked Technical Questions
What is AOD-9604?
AOD-9604 is a synthetic 16-amino-acid peptide derived from the C-terminal region of growth hormone, with an additional N-terminal tyrosine and an internal disulfide bond.
What is the amino acid sequence of AOD-9604?
YLRIVQCRSVEGSCGF.
How many amino acids are in AOD-9604?
AOD-9604 contains 16 amino acid residues.
What is the molecular formula of AOD-9604?
C₇₈H₁₂₃N₂₃O₂₃S₂.
What is the molecular weight of AOD-9604?
Approximately 1,815.1 g/mol.
What is the CAS number?
221231-10-3.
What is the PubChem CID?
Is AOD-9604 identical to full-length growth hormone?
No. AOD-9604 is a short synthetic fragment analog, while mature growth hormone contains 191 amino acid residues.
Is AOD-9604 the same as native hGH fragment 176–191?
Not exactly. AOD-9604 contains an N-terminal tyrosine followed by residues corresponding to hGH positions 177–191.
Does AOD-9604 contain a disulfide bond?
Yes. Cysteine residues at positions 7 and 14 form an intramolecular disulfide bridge.
Is AOD-9604 a cyclic peptide?
It contains a cyclic region formed by a disulfide bond, but its backbone is not fully head-to-tail cyclized.
What is the purpose of the N-terminal tyrosine?
It is a structural modification that distinguishes AOD-9604 from the corresponding native fragment and influences its chemical identity and properties.
Does AOD-9604 activate the growth hormone receptor?
Published experimental findings did not demonstrate conventional growth hormone receptor binding or receptor-mediated proliferation under the conditions examined.
What is the primary receptor of AOD-9604?
A definitive primary receptor has not been established.
Why is the disulfide bond important for analytical testing?
Its presence changes the peptide’s covalent structure and molecular mass relative to the reduced form.
Can mass spectrometry identify AOD-9604?
Mass spectrometry can provide evidence of a molecular mass consistent with the reference structure.
Does mass spectrometry prove the correct disulfide connection?
Not necessarily. Additional structural analysis may be required.
What does HPLC measure?
HPLC separates chemical components and can provide chromatographic purity information.
Is 99% HPLC purity the same as 99% peptide content?
No. They represent different analytical properties.
Can AOD-9604 undergo degradation?
Yes. Like other peptides, AOD-9604 may undergo chemical or physical changes depending on its environment.
Is AOD-9604 FDA-approved?
No. AOD-9604 is not an FDA-approved drug substance.
12. Scientific References and Technical Resources
Chemical Structure and Molecular Identity
PubChem: AOD-9604
Reference information: Molecular formula, molecular weight, amino acid sequence, CAS number, and disulfide-linked structure.
Original Fragment-Related Experimental Research
Ng F.M. et al. (2001)
Metabolic Studies of a Synthetic Lipolytic Domain (AOD9604) of Human Growth Hormone.
Journal: Hormone Research
Technical relevance: Early experimental characterization of the synthetic growth hormone fragment analog.
Growth Hormone Receptor Investigation
Heffernan M.A. et al. (2001)
Increase of Fat Oxidation and Weight Loss in Obese Mice Caused by Chronic Treatment with Human Growth Hormone or a Modified C-Terminal Fragment.
Journal: International Journal of Obesity
Technical relevance: Includes laboratory experiments examining growth hormone receptor binding and receptor-associated cellular responses.
Additional Molecular Pathway Research
Heffernan M.A. et al. (2001)
The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice and β3-AR Knock-Out Mice.
Journal: Endocrinology
Technical relevance: Experimental investigation of pathways associated with the peptide fragment.
https://doi.org/10.1210/endo.142.12.8522
FDA Chemical Characterization Review
FDA: AOD-9604-Related Bulk Drug Substances — Scientific Briefing (2024)
Technical relevance: Chemical identity, structural considerations, peptide-related impurities, and characterization challenges.
Conclusion
AOD-9604 is a synthetic 16-residue peptide whose structure originates from the C-terminal region of growth hormone.
Its defining chemical characteristics include an additional N-terminal tyrosine, a disulfide bridge between Cys7 and Cys14, and a free C-terminal carboxyl group.
These features distinguish it from the native growth hormone fragment and from GHRH-related peptides such as Sermorelin and Tesamorelin.
From a technical perspective, AOD-9604 is particularly relevant to the study of peptide-fragment architecture, disulfide chemistry, molecular identification, chromatographic analysis, and stability.
Its covalent structure must be considered when interpreting molecular mass measurements and analytical documentation.
Accurate research characterization requires distinguishing the defined reference molecule from the chemical and physical properties of an individual sample.
Technical research notice: This resource is intended for educational discussion of peptide chemistry, molecular structure, and analytical research. It does not contain administration, dosing, or medical-use instructions. AOD-9604 is not FDA-approved, and analytical documentation does not establish the suitability of a research material for human or veterinary use.
