title: Solid-phase guanidinylation of peptidyl amines compatible with standard Fmoc-chemistry: formation of monosubstituted guanidines.
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.
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Bionda
authors.forename: Predrag
authors.initials: P
authors.lastname: Cudic
mesh_terms: D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry; D055666:Lipopeptides / Q000138:chemical synthesis; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000588:Amines; D000596:Amino Acids; D005449:Fluorenes; D006146:Guanidines; D055666:Lipopeptides; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D010456:Peptides, Cyclic