Solid-Phase Guanidinylation of Peptidyl Amines Compatible with Standard Fmoc-Chemistry: Formation of Monosubstituted Guanidines

  • Nina Bionda
  • Predrag Cudic
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1081)

Abstract

With the growing importance of peptides and peptidomimetics as potential therapeutic agents, a continuous synthetic interest has been shown for their modification to provide more stable and bioactive analogs. Among many approaches, peptide/peptidomimetic guanidinylation offers access to analogs possessing functionality with strong basic properties, capable of forming stable intermolecular H-bonds, charge pairing, and cation-π interactions. Therefore, guanidinium functional group is considered as an important pharmacophoric element. Although a number of methods for solid-phase guanidinylation reactions exist, only a few are fully compatible with standard Fmoc solid-phase peptide chemistry.

In this chapter we summarize the solid-phase guanidinylation methods fully compatible with standard Fmoc-synthetic methodology. This includes use of direct guanidinylating reagents such as 1-H-pyrazole-1-carboxamidine and triflylguanidine, and guanidinylation with di-protected thiourea derivatives in combination with promoters such as Mukaiyama’s reagent, N-iodosuccinimide, and N,N′-diisopropylcarbodiimide.

Key words

Guanidinylation Fmoc solid-phase peptide synthesis Depsipeptides Triflylguanidine 1-H-pyrazole-1-carboxamidine Thiourea Mukaiyama’s reagent N-Iodosuccinimide N,N′-Diisopropylcarbodiimide 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nina Bionda
    • 1
  • Predrag Cudic
    • 1
  1. 1.Torrey Pines Institute for Molecular StudiesPort St. LucieUSA

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