Short Peptide Synthesis

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Liquid phase peptide synthesis (LPPS) for short dipeptides or tripeptides

Liquid-phase peptide synthesis is a classical method that is still commonly used for the large-scale synthesis of small peptides such as dipeptides or tripeptides. This method benefits from the highly specific reaction, avoiding substrate side chain protection, and the racemate-free formation of products. However, this method is slow and labor-intensive because the product has to be removed from the reaction solution manually after each step. in addition, it requires an additional chemical group to protect the C-terminus of the first amino acid. The most common procedure for peptide synthesis remains solid phase peptide synthesis (SPPS).

The strategy for Liquid Phase Synthesis

For any scale of SPPS, the purification costs drive the manufacturing cost. LifeTein's PeptideSyn technology is optimized to reduce purification costs, include optimizing the stationary and mobile phases, the recycling of solvents, controlling the process parameters, and product yield.

Before planning solution phase peptide synthesis, LifeTein's PeptideSyn platform will automatically select the correct C-terminal protecting group, N terminal group, R group, or coupling reagent according to the sequence of the peptide. This achieves a robust and cost-effective manufacturing process. The most common amino acid-protecting group used is methy ester because it is stable in most coupling and deprotection reaction conditions. Allyl ester can also be used depending on the type of coupling reaction. In addition, Boc and Fmoc groups, as well as Cbz or Nosyl groups can be used. Some of the R-groups that must be protected before coupling are hydroxyl groups (Ser), thiols (Cys), amines (Lys), and carboxylic acids (Asp). By optimizing a number of variables, LifeTein is able to synthesize difficult peptides in less time and using shorter reaction times using the PeptideSyn system.

Pros
  • Method of choice for the production of short peptides < 10 amino acids
  • Unlimited capacity from grams to kilograms
  • Limited impurities
  • Low cost of raw materials
Cons
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  • Labor intensive with two isolation steps per amino acid addition
  • Only a limited number of amino acids can combine
  • Convergent synthesis
  • Long cycle time and low yield
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