Synthesis of novel protected Nα(ω-thioalkyl) amino acid building units and their incorporation in backbone cyclic disulfide and thioetheric bridged peptides

G. Gellerman, C. Gilon, E. Glukhov, S. Gazal

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

27 اقتباسات (Scopus)

ملخص

General methods for the preparation of protected Nα(ω-thioalkyl) amino acids building units for backbone cyclization using reductive alkylation and on-resin preparation are described. The synthesis of non-Gly Fmoc-protected S-functionalized N-alkylated amino acids is based on the reaction of readily prepared protected ω-thio aldehyde with the appropriate amino acid. Preparation of Fmoc-protected S-functionalized N-alkylated Gly building units was carried out using two methods: reaction of glyoxylic acid with Acm-thioalkylamine and an on-resin reaction of bromoacetyl resin with Trt-thioalkylamines. Three model peptides were prepared using these building units. The GlyS2 building unit was incorporated into a backbone cyclic analog of somatostatin that contains a disulfide bridge. Formation of the disulfide bridge was performed by on-resin oxidation using l2 or TI(CF3COO-)3. Both methods resulted in the desired product in a high degree of purity in the crude. The AspS3 building unit was also successfully incorporated into a model peptide. In addition, the in situ generation of sulfur containing Gly building units was demonstrated on a Substance P backbone cyclic analog containing a thioether bridge.

اللغة الأصليةالإنجليزيّة
الصفحات (من إلى)527-539
عدد الصفحات13
دوريةJournal of Peptide Research
مستوى الصوت58
رقم الإصدار6
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 2001
منشور خارجيًانعم

بصمة

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