PAM Resin
PAM resin has become the most widely used resin in Boc chemistry peptide synthesis. It has
greater acid stability than Merrifield resin, making it suitable for synthesizing medium and large
peptides.
The first amino acid is attached to PAM resin using an activating agent such as
dicyclohexylcarbodiimide (DCC) and a catalytic amount of 4-dimethylaminopyridine (DMAP).
These conditions can lead to partial epimerization of the amino acid, so HOBt is normally added to
reduce racemization. The remainder of the peptide can be prepared using standard coupling
conditions. The completed peptide can be deprotected and cleaved from the resin simultaneously
with HF. HF is highly toxic, volatile and corrosive and must be used in a special HF-resistant
apparatus. Alternative cleavage protocols using TFMSA or TMSOTf have been developed,
however these may require multiple steps to remove all side chain protecting groups.
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