Improved Synthesis with Dmb-Glycine Dipeptide Building Blocks

Published on 02/02/2015

Positions next to Glycine are often reasons for side reactions, as aspartamide or diketopiperazine formation can occur. Dmb and Tmb can be used for temporary protection of the amide nitrogen of a peptide bond, in order to solubilize the peptide and increase yield and purity.

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.

Internal solubilisation during peptide synthesis

✓ 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

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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.
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