Abstract
Functions and properties of native peptides vary from highly specific antibiotics or cytotoxic antitumor drugs, to hormones, neurotransmitters, immunomodulators, etc. Despite their potential utility as therapeutic agents, there are problems connected with the use of natural peptides, due to the low stability against proteolysis, resulting in a short duration of in vivo activity, and in a low bioavailability. One way to overcome these disadvantages is the use of modified peptides, the so called peptidomimetics. Overall, the less peptide character in a drug candidate, the more stable it is towards protease cleavage. A huge number of non-peptidic scaffolds have been reported in the literature; nevertheless, several cases have failed to reproduce the activity of the precursor peptide when the scaffold itself contains relevant pharmacophore elements. Therefore, quasi-peptides still maintain their appeal for applications in medicinal chemistry. For the large number of different unnatural amino acids and peptidomimetics, the overview cannot be all-inclusive. This review focuses on modified peptides in which the peptide character is still preponderant, with particular emphasis on the chemical methodologies utilized to introduce the modifications.
Keywords: Peptidomimetic, unnatural amino acid, isoster, scaffold, enzymatic degradation, metabolism, cyclopeptide
Current Pharmaceutical Design
Title: Chemical Modifications Designed to Improve Peptide Stability: Incorporation of Non-Natural Amino Acids, Pseudo-Peptide Bonds, and Cyclization
Volume: 16 Issue: 28
Author(s): Luca Gentilucci, Rossella De Marco and Lucia Cerisoli
Affiliation:
Keywords: Peptidomimetic, unnatural amino acid, isoster, scaffold, enzymatic degradation, metabolism, cyclopeptide
Abstract: Functions and properties of native peptides vary from highly specific antibiotics or cytotoxic antitumor drugs, to hormones, neurotransmitters, immunomodulators, etc. Despite their potential utility as therapeutic agents, there are problems connected with the use of natural peptides, due to the low stability against proteolysis, resulting in a short duration of in vivo activity, and in a low bioavailability. One way to overcome these disadvantages is the use of modified peptides, the so called peptidomimetics. Overall, the less peptide character in a drug candidate, the more stable it is towards protease cleavage. A huge number of non-peptidic scaffolds have been reported in the literature; nevertheless, several cases have failed to reproduce the activity of the precursor peptide when the scaffold itself contains relevant pharmacophore elements. Therefore, quasi-peptides still maintain their appeal for applications in medicinal chemistry. For the large number of different unnatural amino acids and peptidomimetics, the overview cannot be all-inclusive. This review focuses on modified peptides in which the peptide character is still preponderant, with particular emphasis on the chemical methodologies utilized to introduce the modifications.
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Cite this article as:
Gentilucci Luca, De Marco Rossella and Cerisoli Lucia, Chemical Modifications Designed to Improve Peptide Stability: Incorporation of Non-Natural Amino Acids, Pseudo-Peptide Bonds, and Cyclization, Current Pharmaceutical Design 2010; 16 (28) . https://dx.doi.org/10.2174/138161210793292555
DOI https://dx.doi.org/10.2174/138161210793292555 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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