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

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Peptide Modifications to Increase Metabolic Stability and Activity

Part of the book series: Methods in Molecular Biology ((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.

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Authors and Affiliations

  1. Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, USA

    Nina Bionda & Predrag Cudic

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  1. Nina Bionda
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  2. Predrag Cudic
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  1. Torrey Pines Institute for Molecular Stu, Port St. Lucie, Florida, USA

    Predrag Cudic

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Bionda, N., Cudic, P. (2013). Solid-Phase Guanidinylation of Peptidyl Amines Compatible with Standard Fmoc-Chemistry: Formation of Monosubstituted Guanidines. In: Cudic, P. (eds) Peptide Modifications to Increase Metabolic Stability and Activity. Methods in Molecular Biology, vol 1081. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-652-8_10

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  • DOI: https://doi.org/10.1007/978-1-62703-652-8_10

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-651-1

  • Online ISBN: 978-1-62703-652-8

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