N-[(Phenylmethoxy)carbonyl]-L-valyl-N-[(1S)-3-fluoro-1-(2-methoxy-2-oxoethyl)-2-oxopropyl]-L-alaninamide
[CAS# 187389-52-2]

Identification

• Classification: Biochemical >> Inhibitor >> Apoptosis >> Caspase inhibitor
• Name: N-[(Phenylmethoxy)carbonyl]-L-valyl-N-[(1S)-3-fluoro-1-(2-methoxy-2-oxoethyl)-2-oxopropyl]-L-alaninamide
• Synonyms: PN: WO2005039629 PAGE: 18 claimed protein; 3: PN: WO0158526 SEQID: 3 claimed sequence
• Protein Sequence: VAX
• Molecular Formula: C₂₂H₃₀FN₃O₇
• Molecular Weight: 467.49
• CAS Registry Number: 187389-52-2
• SMILES: C[C@@H](C(=O)N[C@@H](CC(=O)OC)C(=O)CF)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 732.4±60.0 ºC 760 mmHg (Calc.)^*
• Flash point: 396.7±32.9 ºC (Calc.)^*
• Solubility: DMSO 90 mg/mL, Water <1 mg/mL (Expl.)
• Index of refraction: 1.51 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

N-[(Phenylmethoxy)carbonyl]-L-valyl-N-[(1S)-3-fluoro-1-(2-methoxy-2-oxoethyl)-2-oxopropyl]-L-alaninamide is a synthetic dipeptide derivative designed to explore protease inhibition and peptide-related biochemical applications. This compound incorporates protective and functional groups that enhance its stability and biological activity.

The molecule features a phenylmethoxycarbonyl (commonly known as a carbobenzyloxy or Cbz) protecting group on the N-terminus of the L-valyl residue, which is widely used in peptide synthesis to prevent unwanted reactions at the amino group during chain elongation. The presence of the fluorinated substituent, specifically a 3-fluoro group attached to a modified alaninamide moiety, contributes to altered biochemical properties such as increased metabolic stability and potential modulation of enzyme interactions.

The 2-methoxy-2-oxoethyl group attached to the fluorinated center adds further chemical complexity, influencing the molecule’s solubility and steric profile. Such structural features are commonly explored to optimize binding affinity and selectivity in enzyme inhibition studies.

This compound has been utilized in research contexts focused on protease inhibition, where modifying peptide backbones with fluorine-containing groups can enhance resistance to enzymatic degradation and improve pharmacokinetic profiles. Its design allows the evaluation of how fluorinated amino acid analogs affect peptide-enzyme interactions, providing insights relevant for the development of therapeutic agents.

Applications include use as a biochemical tool to study protease specificity and inhibition mechanisms, as well as a potential lead compound for drug development efforts targeting diseases where protease activity is dysregulated. The incorporation of the Cbz group ensures synthetic versatility, allowing further modification or conjugation as needed for experimental purposes.

Overall, N-[(Phenylmethoxy)carbonyl]-L-valyl-N-[(1S)-3-fluoro-1-(2-methoxy-2-oxoethyl)-2-oxopropyl]-L-alaninamide represents a carefully engineered peptide derivative that aids in understanding protease function and designing improved peptide-based inhibitors with enhanced stability and efficacy.

References

2016. Effects of a broad-spectrum caspase inhibitor, Z-VAD(OMe)-FMK, on viral hemorrhagic septicemia virus (VHSV) infection-mediated apoptosis and viral replication. Fish & Shellfish Immunology, 51.
DOI: 10.1016/j.fsi.2016.02.021

2020. Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 117(47).
DOI: 10.1073/pnas.2005463117

2021. A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome. Cell Reports, 35(4).
DOI: 10.1016/j.celrep.2021.109040