Detailed Explanation
Peptide bond formation is thermodynamically unfavorable under standard conditions, so the carboxyl group must be 'activated' — converted into a more reactive species that can be attacked by the amino group of the next residue. Coupling reagents do this job. Modern reagents like HATU (hexafluorophosphate azabenzotriazole tetramethyl uronium) achieve >99.5% coupling efficiency per step, which is critical because even small per-step losses compound: 99% efficiency over 50 steps yields only 60% overall; 99.5% yields 78%. Coupling efficiency, along with deprotection completeness, determines the maximum length of peptide achievable by SPPS — typically about 50–70 residues before yields become impractical.
Key Facts
- Peptide bond formation is thermodynamically unfavorable under standard conditions, so the carboxyl group must be 'activated' — converted into a more reactive species that can be attacked by the amino group of the next residue
- Coupling reagents do this job
- Modern reagents like HATU (hexafluorophosphate azabenzotriazole tetramethyl uronium) achieve >99
- 5% coupling efficiency per step, which is critical because even small per-step losses compound: 99% efficiency over 50 steps yields only 60% overall; 99
- Coupling efficiency, along with deprotection completeness, determines the maximum length of peptide achievable by SPPS — typically about 50–70 residues before yields become impractical
Part of the PeptideBond.com education network