Preparing the resin for cleavage

Before the cleavage reaction can be performed, it is essential that the peptidyl resin is thoroughly washed to remove all traces of DMF, as described in Protocol 1C. 

2 Cleavage reactions releasing fully deprotected peptides 

Owing to the variability in the behaviour of different peptide resins, it is recommended that a preliminary small-scale cleavage of peptide-resin using 20-30 mg sample be carried out to determine the optimum cleavage conditions, such as the choice of scavenger(s) and length of reaction. This will enable the extent of cleavage (e.g. by quantitative analysis of the reference amino acid attached to the linker, where appropriate) and the quality of the crude cleaved peptide (by LC-MS) to be determined. 

Phenol is thou t to offer some protection to Tyr and Trp residues (58). Trialkylsilanes, such as triisopropylsilane (TIS) and triethylsilane (TES), ve been shown to be effective, non-odorous substitutes for EDT (59), particularly for peptides containing Arg(Pmc)/Arg(Pbf) and Trp(Boc) (60, 61). These reagents are also very efficient at quenching highly stabilized cations liberated on cleavage of Trt (59), Tmob (61,62), and the Rink amide linker, and hence their use is strongly recommended when these moieties are present. 

A number of universal cleavage mixtures have been advocated, the most popular of which are Reagent K (TFA/thioanisole/water/phenol/EDT ffi.5 5 5 5 2.5 v/v) and Reagent R (TFA/thioanisole/anisole/EDT 90 5 3 2 v/v) (58). However, with recent developments in protecting group chemistry, in 

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