I want to make fully deprotected peptide attached to the resin, which could be for example used later instead of attaching biotinylated peptide to beads with streptavidin. Is there a suitable resin for me? I'm using standard Fmoc SPPS.
With the Fmoc strategy, you have to use weak bases to remove the Fmoc protecting groups during SPPS. Thus, the side-chain protecting groups need to be stable against bases and are usually selected to be cleaved by acids. To make the final removal step from the resin orthogonal with regard to both these steps, you should use a resin with a linker that can stand both bases and weaker acids. There should be resins available which require cleavage by very strong acids like TFA or HF, or by pH-independent techniques like irradiation or reduction. Another strategy would be the other way round by using unusual orthogonal side-chain protecting groups that are acic-base stable, which allows you to use an acid-labile resin linker.
Hello David, I would suggest using a usual resin (we're using a lot Fmoc Rink amide aminomethyl-polystyrene resin) but rather choose amino acids where side-chains are protected with groups which can be removed by weaker acid (e.g., trityl group) or hydrazine solution (e.g., ivDde group). However, I would be cautious with using this resin in water-containing mixtures later on: the resin shrinks a lot, so your assay components will not be able to diffuse through the resin bead. During SPPS, your resin is swollen in DMF, so there are functional groups also inside resin beads, not only on the surface of those. Therefore, you will lose a lot of active centres when you use your resin in a solvent where swelling is not favoured.