Fast Fmoc synthesis of hAmylin1-37 with pseudoproline assisted on-resin disulfide formation

J Pept Sci. 2007 Dec;13(12):833-8. doi: 10.1002/psc.909.

Abstract

Human amylin (1-37) and the (1-13) fragment were synthesized with and without pseudoproline dipeptides. Thallium (III) trifluoroacetate, a mild oxidant, was used to cyclize the peptides by forming a disulfide bridge from C(2) to C(7). On the basis of our model studies, incorporation of a pseudoproline dipeptide decreases the amount of time necessary for the crude linear amylin (1-13) to cyclize on the resin. Without pseudoproline dipeptides, the 1-37 crude linear amylin was not pure enough to undergo the cyclization reaction. Following the cyclization studies, the synthesis time of the linear human amylin (1-37) was systematically reduced from 58 h to 8.5 h by shortening the reaction times. Cyclization and cleavage times were also reduced to 1.5 h.

MeSH terms

  • Amino Acids / chemistry*
  • Amyloid / chemical synthesis*
  • Amyloid / chemistry
  • Chromatography, High Pressure Liquid / methods
  • Cyclization
  • Disulfides / chemical synthesis*
  • Disulfides / chemistry
  • Fluorenes / chemistry*
  • Fluoroacetates
  • Humans
  • Islet Amyloid Polypeptide
  • Molecular Conformation
  • Oligopeptides / chemistry
  • Proline / analogs & derivatives*
  • Proline / chemistry
  • Stereoisomerism
  • Thallium
  • Thiazoles / chemistry*
  • Time Factors
  • Trifluoroacetic Acid / chemistry

Substances

  • Amino Acids
  • Amyloid
  • Disulfides
  • Fluorenes
  • Fluoroacetates
  • Islet Amyloid Polypeptide
  • N(alpha)-fluorenylmethyloxycarbonylamino acids
  • Oligopeptides
  • Thiazoles
  • pseudoproline
  • thallium trifluoroacetate
  • Proline
  • Thallium
  • Trifluoroacetic Acid