Why is solid phase peptide synthesis limited to 70 amino acids? I'm reading document about Solid phase protein synthesis (SPPS) from Wikipedia, and according to the document:


  SPPS is limited by yields, and typically peptides and proteins in the
  range of 70 amino acids are pushing the limits of synthetic
  accessibility. Synthetic difficulty also is sequence dependent;
  typically amyloid peptides and proteins are difficult to make. Longer
  lengths can be accessed by using native chemical ligation to couple
  two peptides together with quantitative yields.


I'm a bit not understanding why this synthesis method is limited to 70 amino acids in length. Anyone please help me to explain what is the issue?
The issue is one of yield. Each step has a certain yield percentage of yield, that the synthesizers will maximize as much as possible. However, given that it is fairly impossible to generate 100% yield all the time, the amount of desired protein you get over time will deteriorate exponentially with length.

For example, say that each step gives you 95% yield. If you have a protein that is ten amino acids long, your final step will give you .95^10 yield, which is about 60%. 

However, with the same yield per step, but a 70 amino acid chain, the amount of protein you want drops to 2%.

Even if you are at 99% yield per step (a difficult feat), your final yield will be under 50% for a 70 amino acid chain.