New segment synthesis of alpha-inhibin-92 by the acyl disulfide method.
The thiocarboxyl group reacts with diaryl disulfides to give an unsymmetrical acyl disulfide in dimethylformamide (DMF) and a symmetrical diacyl disulfide in aqueous DMF. Both acyl disulfides react with the alpha-amino group to form the peptide bond. The method was used in a new segment synthesis of alpha-inhibin-92 (alpha-IB-92) with use of 2,2'-dipyridyl disulfide as activator. Thiocarboxyl peptides were synthesized by the solid-phase method on 4-[alpha-(Boc-Gly-S)benzyl]phenoxyacetamidomethyl-resin. The segments alpha-IB-92-(1-34)SH (I), Msc-alpha-IB-92-(35-65)SH (II), Msc-alpha-IB-92(66-92)OH (III), and Msc-alpha-IB-92-(35-92)OH (VI) were prepared in yields of 33, 36, 41, and 25%, respectively, with use of crystalline symmetrical anhydrides in double and triple coupling protocols. Segments I, II, and III were used in a 3-segment synthesis of alpha-IB-92 with an overall yield based on starting resin of about 8% while a 2-segment synthesis using I and IV gave 11%. An all stepwise synthesis of alpha-IB-92 gave 4.5%.
Yamashiro
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Laboratory of Molecular Endocrinology, University of California, San Francisco.
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D000595:Amino Acid Sequence; D007202:Indicators and Reagents; D007265:Inhibins / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis*
D007202:Indicators and Reagents; D009842:Oligopeptides; D007265:Inhibins; C051562:alpha-inhibin-92