2,4-Dimethylbenzyl (Dmb) or 2,4,6-Trimethylbenzyl (Tmb) can be used as auxiliary protecting groups for temporarily masking the amide nitrogen of a peptide bond. Furthermore, Dmb and Tmb amino acids prevent aggregation during solid phase synthesis, prevent aspartimide formation when introduced before an Asp residue and disrupt aggregation like pseudoprolines. They can also increase peptide cyclization efficiency.

For ease of synthesis, new dipeptide building blocks can be used to couple two amino acids with one process. Acidic deprotection methods as normally applied on Wang resin finally generate the native sequence.

• ✓ Suppressing side reactions like aspartamide formation
• ✓ Increasing solubility
• ✓ Preventing aggregation
• ✓ Increasing peptide cyclization efficiency

Coupling & Deprotection:

Standard coupling protocols can be applied with reagents such as PyBOP, DIC/HOBt or HATU. Acidic deprotection methods normally used with Wang resin finally generate the native sequence.

References

• N,O-bisFmoc derivatives of N-(2-hydroxy-4-methoxybenzyl)-amino acids: Useful intermediates in peptide synthesis; T. Johnson, M. Quibell and R. C. Sheppard; Journal of Peptide Science 1995; 1: 11-25. doi:10.1002/psc.310010104
• Backbone protection: synthesis of difficult sequences using N-α-Tmob-protected amino acid; N. Clausen, C. Goldammer, K. Jauch and E. Bayer; Peptides 1996: Proceedings of the 14th American Peptide Symposium; 1996: 71-72.
• Synthesis of Transmembrane Segments of a Voltage-Gated K+-Channel: Prevention of Aggregation by Bulky Solubilising Protecting Groups; K. Jauch, C. Goldammer, N. Clausen and E. Bayer; Peptides 1998: Proceedings of the 24th European Peptide Symposium 1998: 497-498.
• All-L-Leu-Pro-Leu-Pro: a challenging cyclization; M. El Haddadi, F. Cavelier, E. Vives, A. Azmani, J. Verducci and J. Martinez; Journal of Peptide Science 2000; 6: 560-570. doi:10.1002/1099-1387(200011)6:11<560::aid-psc275>3.0.co;2-i
• Efficient synthesis and comparative studies of the arginine and Nω,Nω-dimethylarginine forms of the human nucleolin glycine/arginine rich domain; S. Zahariev, C. Guarnaccia, F. Zanuttin, A. Pintar, G. Esposito, G. Maravić, B. Krust, A. G. Hovanessian and S. Pongor; Journal of Peptide Science 2005; 11: 17-28. doi:10.1002/psc.577