Site selection for Hmb backbone protection

The choice of site for Hmb protection is based on the application of a set of standard considerations of the difhcult peptide being synthesized  

Protection must be implemented prior to aggregation to be effective. 

Backbone protection need only be introduced a maximum of each sixth residue (51, 60, 61). As the synthesis extends this becomes more flexible. Thus for a 20 residue sequence containing no proline residues, a maximum of 2 or 3 Hmb residues are reqixired located approximately at residues 5-8 and 12-15. 

The amide bond to be protected needs to be compatible with Hmb chemistry. The main restriction here is that incoming -branched residues (Val, He, Thr) do not couple quantitatively to Hmb residues other than glycine. All other combinations may be protected. 

Aspartyl bonds prone to base-catalysed transformations, e.g. Asp(O Bu)-Asn or Asp(0 Bu)-Gly, require protection (62). 

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