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Peptides and Peptidomimetics: From Synthesis to Applications

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Special Issue Editors

Prof. Dr. Maria Luisa Gelmi

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Guest Editor

DISFARM-Sez, Chimica Generale e Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milano, Italy
Interests: non-coded amino acid synthesis; peptidomimetics; peptide nanomaterials; heterocycles; peptides for biological applications; conformational analysis of peptides

Dr. Sara Pellegrino

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Guest Editor

DISFARM-Sez, Chimica Generale e Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milano, Italy
Interests: protein/protein interaction modulators; nanomaterials; conformational analysis; chemical synthesis of protein domains; peptidomimetics

Special Issue Information

Dear Collegaues,

In recent years, significant attention has been devoted to peptides/peptidomimetics due to their modular nature, structural diversity, biocompatibility, relative chemical and physical stability, and synthetic accessibility. The chemical diversity of single amino acids as well as their ability to generate H-networks depending on their structure allows a variety of complex, different-shaped architectures to be obtained. In fact, linear and cyclic non-coded amino acids, even in short peptide sequences, can provide conformationally stable constrained 3D structural platforms. They are indeed valuable tools when inserted in peptide sequences. Of relevance, in biomedicine, peptidomimetics can be used to define the residues and secondary structures responsible for binding recognition and affinity, and can induce an increased stability to proteolysis. On the other hand, peptidomimetics can be used both as soft materials or hybrid nanomaterials in nano-size delivery systems for different molecules such as anticancer agents, oligonucleotides, antibodies, and proteins. Another interesting application of peptidomimetics is the design of hybrid metal–peptide catalysts through reproduction of the spatial arrangement of functional groups of a catalytic site of a protein.

Prof. Maria Luisa Gelmi
Assoc. Prof. Sara Pellegrino
Guest Editors

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Keywords

non-coded amino acids
peptidomimetics
conformational studies
peptide nanomaterials
peptides for biological applications
peptide and catalysts
molecular modelling

Published Papers (2 papers)

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Research

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20 pages, 3463 KiB

Open AccessArticle

Pharmacological Characterization of µ-Opioid Receptor Agonists with Biased G Protein or β-Arrestin Signaling, and Computational Study of Conformational Changes during Receptor Activation

by Justyna Piekielna-Ciesielska, Roberto Artali, Ammar A. H. Azzam, David G. Lambert, Alicja Kluczyk, Luca Gentilucci and Anna Janecka

Molecules 2021, 26(1), 13; https://doi.org/10.3390/molecules26010013 - 22 Dec 2020

Cited by 8 | Viewed by 3158

Abstract

In recent years, G protein vs. β-arrestin biased agonism at opioid receptors has been proposed as an opportunity to produce antinociception with reduced adverse effects. However, at present this approach is highly debated, a reason why more information about biased ligands is required. While the practical relevance of bias in the case of µ-opioid receptors (MOP) still needs to be validated, it remains important to understand the basis of this bias of MOP (and other GPCRs). Recently, we reported two cyclopeptides with high affinity for MOP, the G protein biased Dmt-c[d-Lys-Phe-pCF₃-Phe-Asp]NH₂ (F-81), and the β-arrestin 2 biased Dmt-c[d-Lys-Phe-Asp]NH₂ (C-33), as determined by calcium mobilization assay and bioluminescence resonance energy transfer-based assay. The biased character of F-81 and C-33 has been further analyzed in the [³⁵S]GTPγS binding assay in human MOP-expressing cells, and the PathHunter enzyme complementation assay, used to measure β-arrestin 2 recruitment. To investigate the structural features of peptide-MOP complexes, we performed conformational analysis by NMR spectroscopy, molecular docking, and molecular dynamics simulation. These studies predicted that the two ligands form alternative complexes with MOP, engaging specific ligand–receptor contacts. This would induce different displays of the cytosolic side of the seven-helices bundle, in particular by stabilizing different angulations of helix 6, that could favor intracellular coupling to either G protein or β-arrestin. Full article

(This article belongs to the Special Issue Peptides and Peptidomimetics: From Synthesis to Applications)

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Review

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25 pages, 8158 KiB

Open AccessReview

Revisiting the Self-Assembly of Highly Aromatic Phenylalanine Homopeptides

by Enric Mayans and Carlos Alemán

Molecules 2020, 25(24), 6037; https://doi.org/10.3390/molecules25246037 - 20 Dec 2020

Cited by 21 | Viewed by 2950

Abstract

Diphenylalanine peptide (FF), which self-assembles into rigid tubular nanostructures, is a very short core recognition motif in Alzheimer’s disease β-amyloid (Aβ) polypeptide. Moreover, the ability of the phenylalanine (F or Phe)-homopeptides to self-assemble into ordered nanostructures has been proved. Within this context it was shown that the assembly preferences of this family of compounds is altered by capping both the N- and C-termini using highly aromatic fluorenyl groups (i.e., fluorenyl-9-methoxycarbonyl and 9-fluorenylmethyl ester, named Fmoc and OFm, respectively). In this article the work performed in the field of the effect of the structure and incubation conditions on the morphology and polymorphism of short (from two to four amino acid residues) Phe-homopeptides is reviewed and accompanied by introducing some new results for completing the comparison. Special attention has been paid to the influence of solvent: co-solvent mixture used to solubilize the peptide, the peptide concentration and, in some cases, the temperature. More specifically, uncapped (FF, FFF, and FFFF), N-capped with Fmoc (Fmoc-FF, Fmoc-FFF, and Fmoc-FFFF), C-capped with OFm (FF-OFm), and doubly capped (Fmoc-FF-OFm, Fmoc-FFF-OFm, and Fmoc-FFFF-OFm) Phe-homopeptides have been re-measured. Although many of the experienced assembly conditions have been only revisited as they were previously reported, other experimental conditions have been examined by the first time in this work. In any case, pooling the effect of highly aromatic blocking groups in a single study, using a wide variety of experimental conditions, allows a perspective of how the disappearance of head-to-tail electrostatic interactions and the gradual increase in the amount of π–π stacking interactions, affects the morphology of the assemblies. Future technological applications of Phe-homopeptides can be envisaged by choosing the most appropriate self-assemble structure, defining not only the length of the peptide but also the amount and the position of fluorenyl capping groups. Full article

(This article belongs to the Special Issue Peptides and Peptidomimetics: From Synthesis to Applications)

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