Pseudopeptide Synthesis via Fmoc Solid-Phase Synthetic Methodology

Multifaceted Roles of Disulfide Bonds. Peptides as Therapeutics

“…Thus, reduced amide pseudopeptides, 151 azapeptides, 152 retro-inverso and partial retro-inverso peptides, 153,154 depsipeptides, 155 and peptoids 156 are the most commonly explored pseudopeptides and peptidomimetics, although other bioisoster subunits have also been studied (Figure 4). 157,158 Natural constrained peptides, such as small disulfide-rich peptides, have attracted the attention of the peptide chemistry community because of their extraordinary stability and pharmacokinetic profiles. The multiple disulfide bonds present in these privileged peptide sequences give rise to a well-defined and constrained framework, and some of these compounds are considered miniproteins.…”

Solid‐Phase Synthesis of Peptidomimetics with Peptide Backbone Modifications

“…Some examples of these replacement units are illustrated in Figure 9 and include amine moiety substitutes such as depsipeptide and thiodepsipeptide units; carbonyl substitutes include thioamide, sulfono‐, phosphono‐, and boronopeptide units; and Cα amine group substitutions such as azapeptide and azatide units. The key design strategies and synthetic methodologies of amide bond functionality surrogates have been summarized previously [11a–c,79] …”

Peptides and Peptidomimetics in Medicinal Chemistry

“…The backbone of a peptide can be modified in various ways by isosteric or isoeletronic substitution (Cudic & Stawikowski, 2007;and reference therein). Figure 6 summarizes the most important ways to modify the peptide backbone.…”

“…However, such modifications may also have some negative effects on peptides biophysical and biochemical properties, in particular their conformation, flexibility and hydrophobicity. Therefore, the choice of an amide bond surrogate is a compromise between positive effects on pharmacokinetics and bioavailability and potential negative effects on activity and specificity (Cudic & Stawikowski, 2007). The ability of the surrogate to mimic the steric, electronic and solvation properties of the amide bond is certainly the most important characteristic in determining the potency of pseudopeptide analogs.…”