Optimization of physicochemical and pharmacological properties of peptide drugs by glycosylation

Methods Mol Biol. 2013:1081:107-36. doi: 10.1007/978-1-62703-652-8_8.

Abstract

Many biological interactions and functions are mediated by glycans, leading to the emerging importance of carbohydrate and glycoconjugate chemistry in the design of novel drug therapeutics. In addition to direct effects on biological activity, sugar addition appears to alter many physicochemical and pharmacological properties of the peptide backbone. Consequently, glycosylation has been often used to improve various less than optimal features of peptide drug leads.In order to study the effects that naturally occurring and/or nonnatural glycans have on peptide drug solubility, conformation, proteolytic resistance, membrane permeability, and toxicity, it is essential to have convenient synthetic access toward synthesis of glycopeptide analogs. The crucial step in the synthesis of glycopeptides is the introduction of the carbohydrate group. The preformed glycosyl amino acid building block is the most commonly employed approach used in glycopeptide synthesis.In this review, we will describe various synthetic approaches to prepare N- and O-glycopeptides bearing simple monosaccharides as a tool to improve peptide therapeutic efficacy by glycosylation.

Publication types

  • Review

MeSH terms

  • Amino Acids
  • Fluorenes
  • Glycopeptides / chemical synthesis
  • Glycosylation
  • Monosaccharides / chemistry
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Pharmaceutical Preparations / chemical synthesis
  • Pharmaceutical Preparations / chemistry*
  • Solid-Phase Synthesis Techniques

Substances

  • Amino Acids
  • Fluorenes
  • Glycopeptides
  • Monosaccharides
  • N(alpha)-fluorenylmethyloxycarbonylamino acids
  • Peptides
  • Pharmaceutical Preparations