Detailed Explanation
The percentage of desired target peptide successfully obtained from a synthesis run. In solid-phase peptide synthesis (SPPS), yield is determined by cumulative coupling efficiency — even small per-step losses compound dramatically over long sequences. At 99.5% efficiency per coupling step: a 10-mer yields 95%, a 30-mer yields 86%, a 50-mer yields 78%, and a 70-mer yields 70%.
At 99.0% efficiency: a 30-mer drops to 74% and a 50-mer to 60%. This exponential decay is why SPPS is practical only for peptides up to about 50–70 residues. Yield is improved by optimizing coupling reagents (HATU > HBTU > DIC), extending coupling times for difficult sequences, using microwave-assisted synthesis, and employing pseudoproline dipeptides to disrupt on-resin aggregation.
Crude yield must be distinguished from purified yield (after HPLC purification).
Key Facts
- The percentage of desired target peptide successfully obtained from a synthesis run.
- In solid-phase peptide synthesis (SPPS), yield is determined by cumulative coupling efficiency — even small per-step losses compound dramatically over long sequences.
- At 99.5% efficiency per coupling step: a 10-mer yields 95%, a 30-mer yields 86%, a 50-mer yields 78%, and a 70-mer yields 70%.
- At 99.0% efficiency: a 30-mer drops to 74% and a 50-mer to 60%.
- This exponential decay is why SPPS is practical only for peptides up to about 50–70 residues.
- Yield is improved by optimizing coupling reagents (HATU > HBTU > DIC), extending coupling times for difficult sequences, using microwave-assisted synthesis, and employing pseudoproline dipeptides to disrupt on-resin aggregation.
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