Z-Val-Tyr Methyl Ester: Properties, Handling & Research Use

Z-Val-Tyr methyl ester is a benzyloxycarbonyl (Cbz/Z)-protected dipeptide derivative of L-valine and L-tyrosine in which the C-terminal carboxyl group is masked as a methyl ester, making it a versatile building block for solution- and solid-phase peptide synthesis.

Chemical Name

N-Benzyloxycarbonyl-L-valyl-L-tyrosine methyl ester (Z-Val-Tyr-OMe)

SKU / Product Code

V121382

Protecting Group Strategy

N-terminal protected with Z (Cbz) group; C-terminal as methyl ester

Deprotection Conditions

Z group removable by catalytic hydrogenolysis (H₂/Pd-C) or HBr/AcOH; methyl ester cleavable by mild base hydrolysis (e.g., LiOH/THF/H₂O)

Recommended Storage

Store in a cool, dry place away from light; typically 2–8 °C or as specified on the certificate of analysis

Primary Application

Intermediate in peptide synthesis; substrate or reference compound in protease and enzyme studies

Chemical Identity and Structure

Z-Val-Tyr methyl ester (also written Z-Val-Tyr-OMe) is a fully protected dipeptide comprising two proteinogenic amino acids: L-valine at the N-terminus and L-tyrosine at the C-terminus. The alpha-amino group of valine is shielded by a benzyloxycarbonyl (Z or Cbz) carbamate group, one of the most widely employed N-protecting groups in classical peptide chemistry. The carboxylic acid of tyrosine is esterified as the methyl ester, providing protection at the C-terminus while conferring improved solubility in common organic solvents such as dimethylformamide (DMF), dichloromethane (DCM), and ethyl acetate.

The phenolic hydroxyl group of the tyrosine side chain may or may not carry an additional protecting group depending on the synthetic route; researchers should consult the product's certificate of analysis (CoA) for confirmation of the exact structural specification supplied by Aladdin Scientific.

Handling, Solubility, and Storage Guidelines

Solubility: Z-Val-Tyr methyl ester is generally soluble in polar aprotic organic solvents including DMF, DMSO, and DCM. Solubility in water is expected to be low due to the hydrophobic Z group and the methyl ester moiety. Stock solutions are best prepared in DMSO or DMF; if aqueous buffers are required for biological assays, prepare a concentrated organic stock and dilute immediately before use, keeping the final organic solvent concentration below levels that may affect enzyme activity (typically ≤1% v/v DMSO).

Storage: Store the compound in a tightly sealed container under inert atmosphere (argon or nitrogen) in a cool, dry, and dark environment. Refrigeration at 2–8 °C is recommended for short-term storage; for extended shelf life, −20 °C storage may be preferable. Avoid repeated freeze-thaw cycles of dissolved stock solutions.

Handling precautions: Follow standard laboratory safety practices. Wear appropriate personal protective equipment (PPE) including gloves, lab coat, and eye protection. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use. Avoid inhalation of dust and contact with skin or eyes.

Research Applications in Peptide Chemistry

Z-Val-Tyr methyl ester serves several important roles in synthetic and biochemical research:

• Peptide synthesis intermediate: As a fully N- and C-terminally protected dipeptide, Z-Val-Tyr-OMe can be incorporated into longer peptide sequences. Selective deprotection of either terminus allows directional chain elongation in both solution-phase and Fmoc/Boc-based hybrid strategies.
• Enzyme substrate and inhibitor studies: Dipeptide methyl ester derivatives are commonly used as substrates or reference compounds to characterize proteases, peptidases, and other enzymes that recognise Val-Tyr sequences. The Z group modulates binding to the enzyme active site and can influence kinetic parameters.
• Structure-activity relationship (SAR) studies: Val-Tyr-containing peptides have been reported in the literature in the context of bioactive peptides, including those derived from food proteins with potential antioxidant or ACE-inhibitory properties. Z-Val-Tyr-OMe provides a protected, chemically defined analogue for mechanistic investigations.
• Reference standard: The compound can function as a chromatographic or spectroscopic reference standard in assay development and method validation.

Deprotection Protocols

Correct and sequential deprotection is essential when Z-Val-Tyr-OMe is used as a synthetic intermediate. The following general guidelines reflect established peptide chemistry practice:

1. Removal of the Z (Cbz) group: The benzyloxycarbonyl group is most commonly cleaved by catalytic hydrogenolysis using H₂ gas (1–4 atm) over 10% Pd/C in a suitable solvent such as methanol, ethanol, or ethyl acetate at room temperature. Alternatively, HBr in glacial acetic acid (33% v/v) can be used when palladium-sensitive functionality is absent. Reaction progress should be monitored by TLC or HPLC.
2. Hydrolysis of the methyl ester: The C-terminal methyl ester is readily hydrolysed under mild basic aqueous conditions. A typical protocol uses 1–2 equivalents of lithium hydroxide (LiOH) in a THF/H₂O mixture (1:1 v/v) at 0 °C to room temperature, followed by acidification to recover the free acid. Saponification with NaOH or KOH in aqueous methanol is also effective.
3. Orthogonal deprotection: Because the Z and methyl ester groups are removed under chemically distinct conditions (hydrogenolysis vs. base hydrolysis), they can be removed selectively and in either order, enabling flexible synthetic planning.

Always optimise conditions for your specific substrate and downstream application. Residual catalyst or base must be removed before proceeding to coupling steps.

Quality, Purity, and Regulatory Considerations

Aladdin Scientific supplies Z-Val-Tyr methyl ester (SKU: V121382) as a research-grade reagent. Users should refer to the Certificate of Analysis (CoA) accompanying each lot for confirmed purity, appearance, and analytical data (typically HPLC purity, melting point or NMR confirmation).

Intended use: This product is intended for laboratory research use only and is not approved for human therapeutic, veterinary, food, drug, or cosmetic applications. It is the responsibility of the purchasing institution to ensure appropriate licensing and compliance with local regulations governing the use of research chemicals.

Lot-to-lot consistency: Verify the CoA for each new lot before use in sensitive assays. Any discrepancy in analytical data compared with previous lots should be communicated to Aladdin Scientific's technical support team.

Disposal: Dispose of waste in accordance with applicable local, regional, and national regulations. Do not dispose of chemical waste via the municipal sewage system.

Frequently asked questions

What solvents are suitable for dissolving Z-Val-Tyr methyl ester?

Z-Val-Tyr methyl ester is generally soluble in polar aprotic organic solvents such as DMSO, DMF, and DCM. Aqueous solubility is expected to be low due to the hydrophobic Cbz group and methyl ester. For biological assays requiring aqueous conditions, prepare a concentrated stock in DMSO and dilute into buffer immediately before use, keeping the organic co-solvent below 1% v/v.

How is the Z (Cbz) protecting group removed from Z-Val-Tyr methyl ester?

The Z (Cbz) group is most efficiently removed by catalytic hydrogenolysis: dissolve the compound in methanol or ethyl acetate, add 10% Pd/C, and stir under a hydrogen atmosphere (1–4 atm) at room temperature until deprotection is complete as judged by TLC or HPLC. Alternatively, treatment with 33% HBr in glacial acetic acid can cleave the Z group when palladium-sensitive moieties are absent in the molecule.

Can Z-Val-Tyr methyl ester be used directly in solid-phase peptide synthesis (SPPS)?

Z-Val-Tyr methyl ester is primarily a solution-phase intermediate. Its use in standard Fmoc-SPPS is limited because SPPS relies on Fmoc N-protection rather than Cbz. However, it can serve as a pre-formed dipeptide building block in hybrid or convergent strategies where the Z group is selectively removed in solution and the resulting free amine is coupled to a resin-bound sequence. Consult published protocols for your specific synthetic target before adapting this compound to solid-phase workflows.

What is the recommended storage temperature for Z-Val-Tyr methyl ester?

The compound should be stored in a sealed container under an inert atmosphere, protected from light and moisture. Refrigeration at 2–8 °C is suitable for short-term storage. For long-term preservation, storage at −20 °C is advisable. Always allow the container to equilibrate to room temperature before opening to prevent moisture condensation on the solid.

Is Z-Val-Tyr methyl ester suitable for use as an enzyme substrate?

Protected dipeptide methyl esters like Z-Val-Tyr-OMe are used in the scientific literature as substrates or reference compounds for proteases and peptidases that recognise Val-Tyr sequences. The Z group at the N-terminus mimics a peptide chain upstream of the scissile bond and can influence enzyme binding. Researchers should validate substrate suitability with kinetic assays under their specific experimental conditions.

References

1. Bodanszky, M. and Bodanszky, A. (1994) The Practice of Peptide Synthesis, 2nd ed. Springer-Verlag, Berlin.
2. Greene, T.W. and Wuts, P.G.M. (2006) Protective Groups in Organic Synthesis, 4th ed. Wiley-Interscience, Hoboken, NJ.
3. Aladdin Scientific Certificate of Analysis, Z-Val-Tyr methyl ester, SKU V121382 (lot-specific; consult current CoA).

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.