Fmoc-Asp(OtBu)-Ser{psi(Me,Me)pro}-OH is an Fmoc-protected Asp-Ser pseudoproline building block for solid-phase peptide synthesis (SPPS). The Ser residue is incorporated in a reversible 2,2-dimethyloxazolidine pseudoproline form that temporarily changes local backbone hydrogen-bonding and conformation during chain elongation.

The preformed Asp-Ser unit introduces the sequence motif in one coupling operation. Under standard TFA-mediated final cleavage and deprotection, the acid-labile pseudoproline ring is opened and the native Ser residue is regenerated.

Product Information

Protected Acidic Side Chain and Pseudoproline

The upstream Asp side-chain carboxyl group is protected as an OtBu ester, while the downstream Ser residue forms the pseudoproline. OtBu prevents side-chain carboxyl reactivity during assembly; the pseudoproline is used to alter local backbone interactions. These are complementary protection functions. For broader process context, see our difficult SPPS troubleshooting.

Use in Difficult Acidic Motifs

For a native Asp-Ser segment, the reagent can introduce the protected acidic residue and the downstream pseudoproline in one coupling step. Its main rationale is sequence-dependent aggregation control, not a blanket claim that pseudoproline eliminates every side reaction associated with Asp/Glu chemistry.

Acidic Cleavage and Native Motif Recovery

Final TFA treatment removes the OtBu ester and opens the pseudoproline ring, restoring the acidic side chain and native Ser. The cleavage cocktail should be selected with the complete sequence and any additional acid-sensitive groups in mind.

Planning Considerations

We would use this building block when the target contains the exact Asp-Ser motif and synthesis behavior suggests a benefit from temporary backbone disruption. Separate controls may still be needed for sequence-specific acid-side-chain reactions and deletion products. Related motifs can be compared in the pseudoproline dipeptide range.

Experimental Planning

When a difficult sequence contains several possible Ser/Thr pseudoproline insertion sites, placement should be assessed together with chain length, hydrophobicity, resin loading, neighboring residues, and the stage at which coupling or deprotection performance begins to decline. The presence of an Asp-Ser motif alone does not establish that this building block is required.

For projects where building-block selection needs to be evaluated with the full target sequence, our sequence-specific peptide synthesis can support integrated planning, synthesis, purification, and QC requirements.

Product Documents

MSDS - Fmoc-Asp(OtBu)-Ser{psi(Me,Me)pro}-OH (AS2086)

The Safety Data Sheet provides product identification, hazard information, handling and storage guidance, exposure controls, transport information, and regulatory information for laboratory use.

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 does psi(Me,Me)pro indicate?

It denotes a dimethyl-substituted pseudoproline formed from the downstream Ser residue. The five-membered oxazolidine temporarily changes backbone behavior during synthesis.

Why is the Asp-Ser unit supplied as a preformed building block?

The amide bond immediately before the pseudoproline nitrogen is already formed, avoiding direct acylation of a sterically hindered oxazolidine nitrogen and allowing the motif to be introduced in one coupling operation.

Does the pseudoproline remain in the final peptide?

No. Standard TFA-mediated final cleavage opens the pseudoproline ring and restores the downstream Ser residue.

Are all protecting groups removed during final cleavage?

The protecting groups used here are acid-labile and are generally removed during TFA-mediated global deprotection, but the final cleavage cocktail should always be chosen for the complete sequence and its full protecting-group pattern.

Research Use Only.