S-Acetamidomethyl group

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. 

Thiol Protectton with the AcETAMiDOMErHYL Group S-Acetamidomethyl-l- 

PS—Cl deprotects cysteine residues protected with trityl, diphenylmethyl, acetamidomethyl, f-butyl, and t-butylsulfenyl groups a mixed disulfide, CyS—S—PS, is obtained, which can form a disulfide with another SH group. Thus it can also be used to form disulfide bonds between two cysteine-containing peptides.  

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. 

S-TriphenylmethyIcysteine is readily oxidized by iodine (MeOH, 25°) to cystine.4 The 5-triphenylmethylcysteine group can be selectively cleaved in the presence Of a — Cys(Acm)— group (Acm = acetamidomethyl).5 5-Benzyl and S-/-butyl thioethers are stable to the action of iodine. 

NO2C6H4SCI, AcOH (results in disulfide formation), followed by NaBHi or HS(CH2)20H or dithioerythritol, quant. 5-Triphenyhnethyl, 5 -4,4-dimethoxy-diphenylmethyl, and S-acetamidomethyl groups are also removed by this method. 

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. 

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