Journal ArticleDOI
Can N-methylated amino acids serve as substitutes for prolines in conformational design of cyclic pentapeptides?
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TLDR
These findings raise the question if it might be possible to replace a proline by an N‐methylated amino acid without altering the desired conformational features, and recovers the side‐chain functionalities.Abstract:
The incorporation of proline into cyclic peptides seems to be the most promising way to induce β-turn structures. Recently, however, it was shown that N-methylated amino acids might be even better suited than proline for introducing turn structures. Another property of proline, the ability to effect cis-peptide bonds, has also been reported for N-methylated amino acids. These findings raise the question if it might be possible to replace a proline by an N-methylated amino acid without altering the desired conformational features. The most important benefit of replacing proline by an N-methylated residue is that one recovers the side-chain functionalities, which could be used for enhancing binding selectivity, or to tune a cyclic peptide concerning its pharmacological properties.
Here, we compare cyclic peptides containing one or two prolines or N-methylated alanines and a combination of both with respect to preferred conformations and cis-peptide bonds. In addition, the positions have been investigated where an N-alkylated amino acid has to be incorporated to mimic structural aspects usually introduced by proline residues. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.read more
Citations
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Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes
TL;DR: A new classification of peptidomimetics (classes A–D) is introduced that enables a clear assignment of available approaches for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.
Journal ArticleDOI
N-methylation of peptides and proteins: an important element for modulating biological functions.
TL;DR: The current knowledge of the versatility of N-methylation in modulating biological, structural, and pharmacokinetic properties of peptides is summarized.
Journal ArticleDOI
Understanding Cell Penetration of Cyclic Peptides.
TL;DR: Common structural features that render most cyclic peptides membrane impermeable, as well as the unique features that allow the minority of sequences to enter the cell interior by passive diffusion, endocytosis/endosomal escape, or other mechanisms are examined.
Journal ArticleDOI
Peptoids and Polypeptoids at the Frontier of Supra- and Macromolecular Engineering.
Journal ArticleDOI
Intestinal permeability of cyclic peptides: common key backbone motifs identified.
Johannes G. Beck,Jayanta Chatterjee,Burkhardt Laufer,Marelli Udaya Kiran,Andreas O. Frank,Stefanie Neubauer,Oded Ovadia,Sarit Greenberg,Chaim Gilon,Amnon Hoffman,Horst Kessler,Horst Kessler +11 more
TL;DR: The structural similarity of the second template structure with the orally bioavailable somatostatin analog cyclo(-Pro-Phe-NMe-D-Trp-N me-Lys-Thr-Nme-PHe-), and the striking resemblance with both β-turns of the orallyBioavailable peptide cyclosporine A, suggests that the introduction of bioactive sequences on the highly Caco-2 permeable templates may result in potent orally bio available drug
References
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Coherence transfer by isotropic mixing: Application to proton correlation spectroscopy
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Proton and carbon-13 assignments from sensitivity-enhanced detection of heteronuclear multiple-bond connectivity by 2D multiple quantum NMR
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Structure determination of a tetrasaccharide: transient nuclear Overhauser effects in the rotating frame
Book ChapterDOI
Turns in peptides and proteins.
TL;DR: The aim of this chapter is to examine structural and functional roles of turns in peptides and proteins.
Journal ArticleDOI
Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis
TL;DR: In this article, the authors present an automated solid-phase method for the synthesis of oligo(N-substituted glycines) (NSGs) which is general for a wide variety of side-chain substituents and allows the rapid synthesis of molecules of potential therapeutic interest.