Peptide-Based Drug Design

11
Preparation of Glycosylated Amino Acids Suitable
for Fmoc Solid-Phase Assembly
Mare Cudic and Gayle D. Burstein
Summary
Many biological interactions and functions are mediated by glycans, consequently
leading to the emerging importance of carbohydrate and glycoconjugate chemistry in the
design of novel drug therapeutics. Despite the challenges that carbohydrate moieties bring
into the synthesis of glycopeptides and glycoproteins, considerable progress has been made
during recent decades. Glycopeptides carrying many simple glycans have been chemically
synthesized, enzymatic approaches have been utilized to introduce more complex
glycans, and most recently native chemical ligation has enabled synthesis of glycoproteins
from well-designed peptide and glycopeptide building blocks. Currently, general
synthetic methodology for glycopeptides relies on preformed glycosylated amino acids
for the stepwise solid-phase peptide synthesis. The formation of glycosidic bonds is of
fundamental importance in the assembly of glycopeptides. As such, every glycosylation
has to be regarded as a unique problem, demanding considerable systematic research. In
this chapter we will summarize the most common chemical methods for the stereoselective
synthesis of N- andO-glycosylated amino acids. The particular emphasis will be given to
the preparation of building blocks for use in solid-phase glycopeptide synthesis based on
the 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategy.
Key Words: Glycosylation; N-andO-glycosylated amino acids; solid-phase synthesis;
glycopeptide; Fmoc approach.
1. Introduction
Glycopeptides are a rapidly growing family of molecules which contain a
carbohydrate domain and a peptide domain. They are the product of a post- or
From: Methods in Molecular Biology, vol. 494: Peptide-Based Drug Design
Edited by: L. Otvos, DOI: 10.1007/978-1-59745-419-3 11, © Humana Press, New York, NY
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