Merrifield solid-phase synthesis

RB Merrifield. Solid-phase synthesis. III. An improved synthesis of bradykinin. 

A number of approaches may be adopted to achieve chemical synthesis of a peptide. The Merrifield solid phase synthesis method is perhaps the most widely used. This entails sequential addition of amino acids to a growing peptide chain anchored to the surface of modified polystyrene beads. The modified beads contain reactive chloromethyl (—CH2CI) groups. 

Probtom 21.30 Describe the Merrifield solid-phase synthesis when carried out in the reverse order of the classical Sanger and Edman methods. <... 

Peptides of 33 amino acid residues in length were synthesized on a Milligen Biosearch 9600 automated peptide synthesizer. The procedures used were based on Merrifield solid phase synthesis utilizing Fmoc-BOP chemistry [38] as described by Mayo et al. [36]. 

Rapid Synthetic Procedures. The most interesting development of the year v/as the skillful use of a-amino acid N-carboxyanhydrides in a rapid synthesis in aqueous medi mi32. This procedure is much faster than the Merrifield "solid phase" synthesis, vmdoubtedly more econoraical, and probably easier to adapt to larger scale syntheses. It appears that more byproducts are formed, but both methods require chroniatographic or more elaborate purification of the final products. 

The method bears many similarities to the Merrifield solid-phase synthesis of peptides. A starter unit is attached to a solid support, nucleosides are attached one-by-one until the sequence is complete, whereupon the target oligonucleotide is removed from the support and purified. 

Write out all of the steps in a Merrifield solid-phase synthesis of Leu—Pro. 

RB Merrifield. Solid phase synthesis (Nobel Lecture). Angew Chem 97 801, 1985. HM Geysen, RH Meloen, SJ Bartelig. Use of peptide synthesis to probe viral antigens for epitopes ta resolution of a single amino acid. Proc Natl Acad Sci USA 81 3998-4002, 1984. 

Mercaptoethanol was incorporated into the Boc removal solution for tryptophan protection in a Merrifield solid-phase synthesis of hen egg white lysozyme, but the reagent proved unsatisfactory. The problem with the reagent was traced to its polymerization, presumably by HS-3 participation [Eq. (45) and Scheme 2]. 

The support used for the Merrifield solid-phase synthesis is a chloromethylated polystyrene resin. 

R. B. Merrifield, Solid-phase synthesis (Nobel lecture). Angew. Chem. Int. Ed. Engl. 1985, 24, 799-810. 

Of the three above-mentioned major classes of natural biopolymers, chemical synthesis of nucleic adds (in particular DNA) and proteins had already been achieved by the Merrifield solid-phase synthesis method a computer-controlled automated synthesizer became commerdally available more than 20 years ago. However, the chemical synthesis of polysaccharides like cellulose was far more difficult than that of the former two classes. Polysaccharide synthesis is the repetition of glycosylation, the most fimdamental reaction in carbohydrate chemistry (Scheme 2). 

Cbz-Gly-Ala-OCHzCgHj + CgHnNHCNHCgHn 11. Merrifield Solid-Phase Synthesis (Section 26-7)... 

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