Total synthesis of the α-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone

J Am Chem Soc. 2012 Feb 22;134(7):3532-41. doi: 10.1021/ja2111459. Epub 2012 Feb 6.

Abstract

Described herein is the first total chemical synthesis of the unique α-subunit of the human glycoprotein hormone (α-hGPH). Unlike the biologically derived glycoprotein hormones, which are isolated as highly complex mixtures of glycoforms, α-hGPH obtained by chemical synthesis contains discrete homogeneous glycoforms. Two such systems have been prepared. One contains the disaccharide chitobiose at the natural N-glycosylation sites. The other contains dodecamer oligosaccharides at these same sites. The dodecamer sugar is a consensus sequence incorporating the key features associated with human glycoproteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Chemistry Techniques, Synthetic
  • Disaccharides / chemical synthesis
  • Disaccharides / chemistry
  • Follicle Stimulating Hormone, Human / chemical synthesis*
  • Follicle Stimulating Hormone, Human / chemistry
  • Glycoprotein Hormones, alpha Subunit / chemical synthesis*
  • Glycoprotein Hormones, alpha Subunit / chemistry
  • Glycosylation
  • Humans
  • Models, Molecular
  • Molecular Sequence Data

Substances

  • Disaccharides
  • Follicle Stimulating Hormone, Human
  • Glycoprotein Hormones, alpha Subunit
  • chitobiose