Peptidomimetics: Fmoc solid-phase pseudopeptide synthesis.
Peptidomimetic modifications or cyclization of linear peptides are frequently used as attractive methods to provide more conformationally constrained and thus more stable and bioactive peptides. Among numerous peptidomimetic approaches described recently in the literature, particularly attractive are pseudopeptides or peptide bond surrogates in which peptide bonds have been replaced with other chemical groups. In these peptidomimetics the amide bond surrogates possess three-dimensional structures similar to those of natural peptides, yet with significant differences in polarity, hydrogen bonding capability, and acid-base character. The introduction of such modifications to the peptide sequence is expected to completely prevent protease cleavage of amide bond and significantly improve peptides' metabolic stability. In this chapter we consider Fmoc solid-phase synthesis of peptide analogs containing the amide surrogate that tend to be isosteric with the natural amide. This includes synthesis of peptidosulfonamides, phosphonopeptides, oligoureas, depsides, depsipeptides, and peptoids.
Cudic
Predrag
P
Department of Chemistry and Biochemistry Florida, Atlantic University, Boca Raton, FL, USA.
Stawikowski
Maciej
M
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry; D014508:Urea / Q000138:chemical synthesis / Q000737:chemistry
D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D013449:Sulfonamides; D014508:Urea