Amino monothio acids in solid-phase synthesis of peptide thioamides.
Peptides containing backbone thioamides (endothiopeptides) have been synthesized utilizing thioacylation under solid-phase conditions. The thioacylations were performed by activating N-protected amino monothio acids with the phosphorus-containing coupling reagent 6-nitrobenzotriazol-l-yloxytris(pyrrolidino)phosphoniu m hexafluorophosphate (PyNOP). This method avoids the use of P4S10-based O/S-exchange reagents, and it is thus amendable to amino acids with side-chain amides. Synthesis of endothio analogs of biologically active peptide such a pGlu-psi [CSNH]-His-Pro-NH2 (TRH) and Leu-Gln-psi [CSNH]-Leu-Lys demonstrated this feature. Proton and carbon NMR spectra of the TRH analog verified the sequential position of its thioamide function. Compatibility of endothiopeptides with allylprotecting groups was studied, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was evaluated as a substitute for piperidine.
Hoeg-Jensen
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Chemistry Department, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Spatola
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AF
Holm
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A
D000215:Acylation; D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D016232:Endothelins / Q000037:antagonists & inhibitors; D005449:Fluorenes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D000072235:Mating Factor; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry; D013854:Thioamides / Q000138:chemical synthesis* / Q000737:chemistry; D013935:Thymic Factor, Circulating / Q000031:analogs & derivatives; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives
D000596:Amino Acids; D016232:Endothelins; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D013854:Thioamides; D013973:Thyrotropin-Releasing Hormone; D000072235:Mating Factor; D013935:Thymic Factor, Circulating; C072247:cyclo(Trp-Asp-Pro-Val-Leu)