Acetamidomethyl protective group

The details of the solid-phase technique have been improved substantially over the years, but the fundamental idea remains the same. The most commonly used resins at present are either the Wang resin or the PAM (phenyl-acetamidomethyl) resin, and the most commonly used N-protecting group is the fluorenylmethyloxycarbonyl, or Fmoc group, rather than Boc. 

DF Veber, JD Milkouski, RG Denkewalter, R Hirschmann. The synthesis of peptides in aqueous solution. IV. A novel protecting group for cysteine. (S-acetamidomethyl) Tetrahedron Lett 3057, 1968. 

SCHEME 11.1 Native chemical ligation and a concept using amino acid having thiol at the (i position. Acm, acetamidomethyl PG, protecting group VA-044,1,2 - azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride. 

Iodinolysis in a protic solvent such as methanol easily cleaves the 5-trityl group and oxidises the liberated thiol to a disulfide. The acetamidomethyl group, another common thiol protecting group (see below), cleaves as well but at a much slower rate when non-polar or weakly nucleophilic solvents such as chloroform. 

The Merck3 total synthesis of ribonuclease involved coupling various peptide units to form a tetrahectapeptide (104 residues) known as S-protein. This polypeptide contains 8 cysteine and 3 methionine residues. The acetamidomethyl blocking group proved invaluable for protection of the cysteine units. 

Dissolve 1 pmol tetrameric peptide possessing an acetamidomethyl (Acm) protecting group in lmL of TFA/anisole (99 1). 

Different protecting groups (S-Trityl, S-Acetamidomethyl...) have been introduced on the cysteine side chains to optimise the reaction conditions of disulfide bridge formation. The conditions developed by Kamber and his group have been used to make the disulfide bridge (ref. 5). The best results have been obtained when we use S trityl on the L-cysteine and S-acetamidomethyl on the 7 cysteine in N,N-dimethylformamide in the presence of an excess of iodine (4 equivalents). The excess of iodine is eliminated with ascorbic acid. The final peptide is isolated by precipitation with water. 

Veber D, Milkowski J, Varga S, Denkewalter R, Hrrschmann R (1972) Acetamidomethyl. A novel thiol protecting group for cysteine. J Am Chtan Soc 94 5456-5461... 

Mercuric acetate (formic acid Acetamidomethyl as S-protective group... 

Primary tritium isotope effect 849 Propellanes, synthesis of 569, 570 Protecting groups for thiols 432 acetamidomethyl 675, 676 acetyl and benzoyl 677, 678 benzyl 671, 672 benzyloxycarbonyl 678 benzylthiomethyl and phenylthio-methyl 681... 

Based on the different chemical activities of 4-methoxyltrityl (Mmt), trityl (Trt) and acetamidomethyl (Acm)-protecting groups we developed two straightforward and easy methods for multiple disulfide bond formation of cysteine-rich peptides using iodine oxidation in solution and solid phase that improve purity of the desired compounds. These methods are applicable to different peptides, such as polyphemusin, endothelin-3, orexin-A and other cysteine-rich peptides. 

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