Fmoc-Ser(tBu)-Thr[psi(Me,Me)Pro]-OH is an Fmoc-protected Ser-Thr pseudoproline building block for solid-phase peptide synthesis (SPPS). The Thr 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 Ser-Thr 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 Thr residue is regenerated.

Product Information

Two Hydroxy Residues, Two Protection Roles

In the Ser-Thr unit, the upstream Ser(tBu) residue carries conventional tert-butyl side-chain protection, while the downstream Thr residue is incorporated as a pseudoproline. The upstream tBu group masks side-chain reactivity; the downstream oxazolidine modifies backbone behavior. This distinction is important when planning deprotection and sequence recovery. This should be considered alongside Fmoc-SPPS workflow when diagnosing sequence-dependent assembly problems.

Application in Ser/Thr-Rich Difficult Sequences

Ser/Thr-rich regions can be highly polar yet still develop sequence-dependent secondary structure on resin. A pseudoproline at the downstream residue can interrupt local backbone organization without permanently modifying the final Ser-Thr sequence.

Final Acid Treatment

Standard TFA-mediated global deprotection removes the tert-butyl ether from the upstream residue and opens the pseudoproline ring at the downstream residue. The final peptide therefore recovers native hydroxyl functionality at both positions, subject to the complete protecting-group pattern of the synthesis.

When This Architecture Is Useful

We consider this reagent when a native Ser-Thr segment is part of a difficult assembly and both side-chain protection and temporary backbone disruption are desired. It is not a generic substitute for ordinary Fmoc-Ser(tBu)-OH or Fmoc-Thr(tBu)-OH in routine sequences. Related motifs can be compared in the related pseudoproline motifs.

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 a Ser-Thr 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 complex peptide synthesis can support integrated planning, synthesis, purification, and QC requirements.

Product Documents

MSDS - Fmoc-Ser(tBu)-Thr[psi(Me,Me)Pro]-OH (AS4030)

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 Thr residue. The five-membered oxazolidine temporarily changes backbone behavior during synthesis.

Why is the Ser-Thr 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 Thr 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.