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(S)-N-Fmoc-α-(4-Pentenyl)Alanine, widely known as Fmoc-S5-OH, is an α-methylated amino acid bearing a terminal alkene. It is designed for Fmoc-SPPS and is commonly used to place an olefin handle at a defined position before on-resin ring-closing metathesis.
The building block is especially relevant to hydrocarbon-stapled peptide design. Two compatible olefin-bearing residues can be positioned in a sequence and later converted into a covalent hydrocarbon bridge. This makes residue spacing, stereochemistry and the surrounding sequence part of the chemistry, not just part of the biological design.
Product Information
| Product Name | (S)-N-Fmoc-α-(4-Pentenyl)Alanine |
| Catalog No. | AS2130 |
| CAS No. | 288617-73-2 |
| Molecular Formula | C23H25NO4 |
| Molecular Weight | 379.45 g/mol |
| Chemical Identity | Fmoc-(S)-2-(4-pentenyl)Ala-OH; Fmoc-S5-OH |
| Building Block Type | Fmoc-protected α-methyl alkenyl amino acid |
| Primary Applications | Hydrocarbon-stapled peptides, ring-closing metathesis, noncanonical peptide SAR and Fmoc-SPPS |
Why Fmoc-S5-OH Is Used for Peptide Stapling
The side chain terminates in an alkene that can undergo olefin metathesis with a second compatible residue. In α-helical designs, S5-type residues are often used in i,i+4 arrangements for a one-turn staple. Staple geometry is not universal, however. Different residue spacing can require different tether lengths or stereochemical combinations. Our peptide cyclization strategy guide compares hydrocarbon stapling with other ways of constraining peptide structure.
Coupling Efficiency Deserves Extra Attention
Fmoc-S5-OH is more sterically demanding than standard alanine because the α-carbon is substituted by both a methyl group and a pentenyl side chain. Difficult incorporation can generate deletion products before the staple is formed. We recommend checking coupling completion at these positions rather than assuming a standard cycle is sufficient. The broader relationship between steric hindrance, resin accessibility and incomplete coupling is covered in our SPPS side-reaction and troubleshooting guide.
Metathesis Success Depends on the Whole Protected Peptide
Two alkenes are necessary but not sufficient for a successful staple. Resin swelling, catalyst access, solvent, protecting groups and catalyst-poisoning functionality can all affect conversion. We consider staple formation a project-level step that should be planned together with chain assembly and purification. This is one reason noncanonical amino-acid selection is most useful when linked to a specific structural objective rather than treated as a generic substitution.
Procurement and QC Considerations
Confirm CAS 288617-73-2, C23H25NO4, MW 379.45 g/mol, S configuration and the terminal-alkene structure. LC-MS confirms mass but does not establish enantiomeric identity. For stapled-peptide work, stereochemistry should be verified because it changes how the tether is presented in three-dimensional space.
Product Documents
A Safety Data Sheet (SDS / MSDS) is available for this product to support laboratory handling, storage and safety assessment.
MSDS_S-N-Fmoc-alpha-4-PentenylAlanine_AS2130
Certificates of Analysis (COAs) are batch-specific. Please contact us to request the COA for your product, and we will provide it by email.
Frequently Asked Questions
What is Fmoc-S5-OH used for?
It introduces an α-methyl 4-pentenyl residue into a peptide, commonly as one half of a hydrocarbon staple.
Why are i and i+4 positions often used?
That spacing approximates one turn of an α-helix and can support an appropriately sized hydrocarbon bridge, although optimal positions remain sequence-dependent.
Can Fmoc-S5-OH be run in a standard Fmoc-SPPS cycle?
Yes, but coupling can be more sterically demanding than with ordinary residues and may require additional monitoring or optimized conditions.
Related Technical Resources
If your project requires sequence-specific staple placement, metathesis and final purification, see our hydrocarbon-stapled and modified peptide synthesis capabilities.