Deprotection of Nin-formyl tryptophan using 1,2-ethanedithiol in liquid hydrogen fluoride. Deformylation upon HF treatment of Merrifield peptidyl-resins.
Deprotection of Nin-formyl tryptophan (Trp) occurs during liquid hydrogen fluoride treatment at 0 degrees when 1,2-ethanedithiol (EDT), or 1,4-butanedithiol, is present. Deformylation, as evidenced by amino acid analysis and ultraviolet spectral analysis, is complete after 10 min at 0 degrees when Trp(CHO) is treated with HF:anisole:EDT(85:10:5) or HF:EDT (95:5). HF treatment of a peptidyl-resin containing Trp(CHO) yielded a peptide whose ultraviolet spectrum was typical of Trp (maximum at 280 nm) rather than Trp(CHO) (maximum at 300 nm). However, in the absence of dithiol during HF treatment, the expected spectrum for Trp(CHO) was obtained. The efficiency of HF cleavage of a 49-peptidyl-resin was unaffected by EDT; 77% was cleaved in the presence of EDT, and 76% in the absence of EDT. In a model study, dithiol deformylation as a synthetic tactic was used for the solid-phase synthesis of Trp-Met-Asp-Phe amide. When the Trp(CHO)-Met-Asp(Bzl)-Phe-NH-methylbenzhydrylamine resin was treated with HF:anisole:EDT(85:10:5) for 30 min at 0 degree, the major peptide component observed by high pressure liquid chromatography (HPLC) was identical to the control tetrapeptide amide made without CHO-group protection of Trp.
D000818:Animals; D005755:Gastrins / Q000138:chemical synthesis; D006858:Hydrofluoric Acid; D036341:Intercellular Signaling Peptides and Proteins; D008623:Mercaptoethanol / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000138:chemical synthesis*; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D012615:Sea Anemones; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000031:analogs & derivatives*
D005755:Gastrins; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; C035643:N-formyltryptophan; D008623:Mercaptoethanol; C012746:anthopleurin-A; D014364:Tryptophan; C031854:1,2-ethanedithiol; D006858:Hydrofluoric Acid