Fmoc-Leu-Thr[psi(Me,Me)pro]-OH is an Fmoc-protected Leu-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 Leu-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

Motif-Specific Role in Aggregation-Prone Sequences

The Leu-Thr motif combines a hydrophobic upstream residue with a Ser/Thr-derived pseudoproline. In hydrophobic or self-associating sequences, temporary backbone disruption can be useful because increasing coupling reagent excess alone does not correct poor resin-bound chain solvation. This should be considered alongside difficult SPPS troubleshooting when diagnosing sequence-dependent assembly problems.

Preformed Dipeptide Coupling Logic

The Leu-Thr bond is preassembled, avoiding direct acylation of the sterically hindered pseudoproline nitrogen. The unit therefore installs both residues while positioning the conformational break at the downstream Thr site.

Cleavage and Sequence Restoration

The pseudoproline is acid-labile. Standard final TFA cleavage opens the ring and restores the native Thr residue, leaving the target Leu-Thr motif in the peptide. Other protecting groups and acid-sensitive modifications in the full sequence should determine the final cleavage formulation.

Practical Selection

We would consider this building block when the Leu-Thr region lies within a long, hydrophobic, beta-sheet-prone, or otherwise difficult sequence. If conventional Fmoc-SPPS already gives clean coupling and deprotection, replacing the motif with a pseudoproline reagent may add complexity without a clear benefit. 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 a Leu-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 sequence-specific peptide synthesis can support integrated planning, synthesis, purification, and QC requirements.

Product Documents

MSDS - Fmoc-Leu-Thr[psi(Me,Me)pro]-OH (AS4028)

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 Leu-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.

Should this be used for every Leu-Thr sequence?

No. Pseudoproline use is most justified when the sequence shows aggregation, poor chain accessibility, or another reproducible assembly problem. Straightforward sequences may not require it.

Research Use Only.