Polystyrene resins, peptide synthesis

The peptide is synthesized on a derivatized solid support, often a polyamide or polystyrene resin, and synthesis proceeds from C-terminus to N-terminus. The linker group, which provides the link between the resin and the peptide... 

The peptide is synthesized on a derivatized solid support, often a polyamide or polystyrene resin, and synthesis proceeds from C-terminus to A -terminus. The linker group, which provides the link between the resin and the peptide chain, varies and depends on the type of C-terminus desired, e.g., C-terminal acid or amide. In addition, resins are available that already have the first protected amino acid attached. This is often desirable, since the bond between the first amino acid and the resin linker is not a peptide bond and therefore, requires a different reaction to the subsequent peptide chain-assembly steps. 

FIGURE 27 14 A section of polystyrene showing one of the benzene rings modified by chloromethylation Indi vidual polystyrene chains in the resin used in solid phase peptide synthesis are con nected to one another at various points (cross linked) by adding a small amount of p divinylbenzene to the styrene monomer The chloromethylation step is carried out under conditions such that only about 10% of the benzene rings bear —CH2CI groups... 

The chloromethylated polystyrene resin used for Merrifteld solid-phase peptide synthesis is prepared by treatment of polystyrene with chloromethyl methyl ether and a Lewis acid catalyst. Propose a mechanism for the reaction. 

The polymeric resin used for Merrifield solid-phase peptide synthesis (Section 26.8) is prepared by treating polystyrene with iV-(hydroxymethyl) phthalimide and trifluoromethanesulfonic acid, followed by reaction with hydrazine. Propose a mechanism for both steps. 

Polystyrene resin with a hydroxymethylphenoxy linker (Wang resin)1 was originally developed for solid-phase peptide synthesis... 

S Zalpsky, JL Chang, F Albericio, G Barany. Preparation and applications of polyethylene glycol-polystyrene graft resin supports for solid-phase peptide synthesis. Reactive Polymers 22, 243, 1994. 

RB Scarr, MA Findeis. Improved synthesis and aminoacylation of p-nitrobenzophe-none oxime polystyrene resin for solid-phase synthesis of protected peptides. Pept Res 3, 238, 1990. 

Synthesis. The synthesis of cyclo retro enantlcxner 6 Is outlined in Scheme 1. Compounds 4, 5, 7> and 9 were prepared by an analogous route. Initially, a protected linear hexapeptide was prepared by solid phase synthesis on 2% crossllnked polystyrene resin beginning with a protected lysine resin. The peptide was then removed from the polymer by hydrazlnolysis. Cycllzatlon was... 

Standard solid-phase peptide synthesis requires the first (C-terminal) amino acid to be esterified with a polymeric alcohol. Partial racemization can occur during the esterification of N-protected amino acids with Wang resin or hydroxymethyl polystyrene [200,201]. /V-Fmoc amino acids are particularly problematic because the bases required to catalyze the acylation of alcohols can also lead to deprotection. A comparative study of various esterification methods for the attachment of Fmoc amino acids to Wang resin [202] showed that the highest loadings with minimal racemization can be achieved under Mitsunobu conditions or by activation with 2,6-dichloroben-zoyl chloride (Experimental Procedure 13.5). iV-Fmoc amino acid fluorides in the presence of DMAP also proved suitable for the racemization-free esterification of Wang resin (Entry 1, Table 13.13). The most extensive racemization was observed when DMF or THF was used as solvent, whereas little or no racemization occurred in toluene or DCM [203]. 

The nature of the polymer support is of great importance for a successful peptide synthesis. One that is widely used is a cross-linked polystyrene resin... 

In the reaction vessel of a Beckman 990 Peptide Synthesizer was placed 0.8 g (0.8 mmol) of benzhydrylamino-polystyrene-divinylbenzene resin (Lab Systems, Inc.) as described by Rivaille, supra. Amino acids were added sequentially to this resin by means of the usual methods of Boc-strategy of peptide synthesis on above copolymer. 

---