Biomimetic Peptides and Proteins

A special issue of Biomimetics (ISSN 2313-7673). This special issue belongs to the section "Biomimetic Processing and Molecular Biomimetics".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 7686

Special Issue Editors


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Guest Editor
Synthetic Biology and Biotechnology Unit, Department of Biology, University of Padua, Padua, Italy
Interests: pandemic viruses; vaccines; synthetic biology and biotechnology; motif identification; protein engineering; biocatalysis; bioremediation; neurodevelopment and neurological disorders; biomimetics and regenerative medicine; subcellular trafficking
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Guest Editor
Laboratory of Protein Chemistry and Molecular Haematology, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
Interests: structural biology; protein engineering; protein chemistry (solid-phase peptide synthesis); enzymology; biochemical and biophysical techniques (surface plasmon resonance; isothermal titration calorimetry; mass spectrometry)

Special Issue Information

Dear Colleagues,

Mimicry is known above all in relation to the world of organisms; however, molecular mimicry is just as widespread. The ability to mimic the functions of some molecules through the engineering of other molecules opened the route to a vast field of research, in both the design and development of biomimetic materials, which are treated in other volumes, and in the field of molecular biomimetics, which are the central topic of this Special Issue.

Proteins are the most versatile functional building blocks of cells and, in turn, are made up of combinations of protein domains, which mediate their interactions and, therefore, their functions.

For biotechnological purposes, the characteristics of proteins and/or their domains can be modified; however, in recent years, synthetic biology and biotechnology have gone further in design and engineering via the concept of functional reprogramming of proteins and protein domains to develop biomimetic molecules. Indeed, a protein or a domain can be attributed by extensive mutagenesis biomimetic characteristics, typical of molecules that are sometimes completely different. A classic example for biomimetic proteins and protein domains are DARPins, in which ankyrin repeat domain loop mutagenesis is used to mimic the hypervariable regions of antibodies and create an antibody-like protein. In general, protein domains in which variable loops are found, and that are easy-to-express, stable and—when needed—immunologically stealthy, are a good starting point for the design of scaffolding proteins, with biomimetic binding features to be used in diagnostics, therapy, biocatalysis, etc.

Protein domains are composed, in turn, of super-secondary structures, of which some mediate interactions crucial to signaling, via intra- and intermolecular binding among linear and or structural epitopes. In several instances, binding regions can be reproduced as synthetic peptides, which are able to mimic or counteract signaling mediated by the whole domain or protein. This allows us to design and develop a plethora of agonist and antagonist peptides, where solid-phase synthesis ensures high yields and a low cost, and allows scientists to be free from troubles with recombinant expression of the whole proteins/domains and their purification.

In addition, the incorporation of non-natural amino acids in synthetic peptidyl scaffolds has improved the field of enzymology and drug discovery. The ability to substitute natural amino acids with non-natural analogues is emerging as a promising approach to elucidate the molecular mechanisms underlying protein folding, stability, and function.

Once relevant binding regions are identified, reproduced as natural sequences of synthetic peptides, and validated for mimicry of a signal-mediating domain/protein, mutant versions can be drawn to design antagonists, and optimization of peptides can be performed to improve stability, delivery, specificity, and biocompatibility.

Dr. Francesco Filippini
Dr. Laura Acquasaliente
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular mimicry
  • protein domain
  • synthetic peptide
  • scaffold protein
  • antibody-like protein
  • loop mutagenesis
  • rational design
  • computational design
  • protein motif
  • agonist
  • antagonist
  • non-natural amino acids
  • synthetic biology
  • structural biology
  • biochemistry
  • solid-phase synthesis
  • binding site

Published Papers (5 papers)

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Research

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13 pages, 2499 KiB  
Article
One-Step Purification of Recombinant Cutinase from an E. coli Extract Using a Stabilizing Triazine-Scaffolded Synthetic Affinity Ligand
by Luís P. Fonseca and M. Ângela Taipa
Biomimetics 2024, 9(1), 57; https://doi.org/10.3390/biomimetics9010057 - 20 Jan 2024
Viewed by 1058
Abstract
Cutinase from Fusarium solani pisi is an enzyme that bridges functional properties between lipases and esterases, with applications in detergents, food processing, and the synthesis of fine chemicals. The purification procedure of recombinant cutinase from E. coil extracts is a well-established but time-consuming [...] Read more.
Cutinase from Fusarium solani pisi is an enzyme that bridges functional properties between lipases and esterases, with applications in detergents, food processing, and the synthesis of fine chemicals. The purification procedure of recombinant cutinase from E. coil extracts is a well-established but time-consuming process, which involves a sequence of two anionic exchange chromatography steps followed by dialysis. Affinity chromatography is the most efficient method for protein purification, the major limitation of its use being often the availability of a ligand selective for a given target protein. Synthetic affinity ligands that specifically recognize certain sites on the surface of proteins are highly desirable for affinity processes due to their cost-effectiveness, durability, and reusability across multiple cycles. Additionally, these ligands establish moderate affinity interactions with the target protein, making it possible to purify proteins under gentle conditions while maintaining high levels of activity recovery. This study aimed to develop a new method for purifying cutinase, utilizing triazine-scaffolded biomimetic affinity ligands. These ligands were previously screened from a biased-combinatorial library to ensure their binding ability to cutinase without compromising its biological function. A lead ligand, designated as 11/3′, [4-({4-chloro-6-[(2-methylbutyl)amino]-1,3,5-triazin-2-yl}amino)benzoic acid], was chosen and directly synthesized onto agarose. Experiments conducted at different scales demonstrated that this ligand (with an affinity constant Ka ≈ 104 M−1) exhibited selectivity towards cutinase, enabling the purification of the enzyme from an E. coli crude production medium in a single step. Under optimized conditions, the protein and activity yields reached 25% and 90%, respectively, with a resulting cutinase purity of 85%. Full article
(This article belongs to the Special Issue Biomimetic Peptides and Proteins)
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12 pages, 2413 KiB  
Article
Biomineralization through a Symmetry-Controlled Oligomeric Peptide
by Tatsuya Sakaguchi, Natsumi Nakagawa, Kenta Mine, Jose Isagani B. Janairo, Rui Kamada, James G. Omichinski and Kazuyasu Sakaguchi
Biomimetics 2023, 8(8), 606; https://doi.org/10.3390/biomimetics8080606 - 14 Dec 2023
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Abstract
Biomineralization peptides are versatile tools for generating nanostructures since they can make specific interactions with various inorganic metals, which can lead to the formation of intricate nanostructures. Previously, we examined the influence that multivalency has on inorganic structures formed by p53 tetramer-based biomineralization [...] Read more.
Biomineralization peptides are versatile tools for generating nanostructures since they can make specific interactions with various inorganic metals, which can lead to the formation of intricate nanostructures. Previously, we examined the influence that multivalency has on inorganic structures formed by p53 tetramer-based biomineralization peptides and noted a connection between the geometry of the peptide and its ability to regulate nanostructure formation. To investigate the role of multivalency in nanostructure formation by biomineralization peptides more thoroughly, silver biomineralization peptides were engineered by linking them to additional self-assembling molecules based on coiled-coil peptides and multistranded DNA oligomers. Under mild reducing conditions at room temperature, these engineered biomineralization peptides self-assembled and formed silver nanostructures. The trimeric forms of the biomineralization peptides were the most efficient in forming a hexagonal disk nanostructure, with both the coiled-coil peptide and DNA-based multimeric forms. Together, the results suggest that the spatial arrangement of biomineralization peptides plays a more important role in regulating nanostructure formation than their valency. Full article
(This article belongs to the Special Issue Biomimetic Peptides and Proteins)
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16 pages, 3165 KiB  
Article
Effect of Bacterial Amyloid Protein Phenol−Soluble Modulin Alpha 3 on the Aggregation of Amyloid Beta Protein Associated with Alzheimer’s Disease
by Bushu Peng, Shaoying Xu, Yue Liang, Xiaoyan Dong and Yan Sun
Biomimetics 2023, 8(6), 459; https://doi.org/10.3390/biomimetics8060459 - 1 Oct 2023
Cited by 1 | Viewed by 1321
Abstract
Since the proposal of the brainstem axis theory, increasing research attention has been paid to the interactions between bacterial amyloids produced by intestinal flora and the amyloid β−protein (Aβ) related to Alzheimer’s disease (AD), and it has been considered as the possible cause [...] Read more.
Since the proposal of the brainstem axis theory, increasing research attention has been paid to the interactions between bacterial amyloids produced by intestinal flora and the amyloid β−protein (Aβ) related to Alzheimer’s disease (AD), and it has been considered as the possible cause of AD. Therefore, phenol−soluble modulin (PSM) α3, the most virulent protein secreted by Staphylococcus aureus, has attracted much attention. In this work, the effect of PSMα3 with a unique cross−α fibril architecture on the aggregation of pathogenic Aβ40 of AD was studied by extensive biophysical characterizations. The results proposed that the PSMα3 monomer inhibited the aggregation of Aβ40 in a concentration−dependent manner and changed the aggregation pathway to form granular aggregates. However, PSMα3 oligomers promoted the generation of the β−sheet structure, thus shortening the lag phase of Aβ40 aggregation. Moreover, the higher the cross−α content of PSMα3, the stronger the effect of the promotion, indicating that the cross−α structure of PSMα3 plays a crucial role in the aggregation of Aβ40. Further molecular dynamics (MD) simulations have shown that the Met1−Gly20 region in the PSMα3 monomer can be combined with the Asp1−Ala2 and His13−Val36 regions in the Aβ40 monomer by hydrophobic and electrostatic interactions, which prevents the conformational conversion of Aβ40 from the α−helix to β−sheet structure. By contrast, PSMα3 oligomers mainly combined with the central hydrophobic core (CHC) and the C−terminal region of the Aβ40 monomer by weak H−bonding and hydrophobic interactions, which could not inhibit the transition to the β−sheet structure in the aggregation pathway. Thus, the research has unraveled molecular interactions between Aβ40 and PSMα3 of different structures and provided a deeper understanding of the complex interactions between bacterial amyloids and AD−related pathogenic Aβ. Full article
(This article belongs to the Special Issue Biomimetic Peptides and Proteins)
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Review

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30 pages, 3473 KiB  
Review
Various Biomimetics, Including Peptides as Antifungals
by Elena Efremenko, Aysel Aslanli, Nikolay Stepanov, Olga Senko and Olga Maslova
Biomimetics 2023, 8(7), 513; https://doi.org/10.3390/biomimetics8070513 - 28 Oct 2023
Cited by 2 | Viewed by 2057
Abstract
Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attraction in the current search for new effective antifungals. Actual trends in the development of this [...] Read more.
Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attraction in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogs; molecules similar to natural substrates of numerous fungal enzymes and quorum-sensing signaling molecules of fungi and yeast, etc. Most parts of this review are devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the current scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects. Full article
(This article belongs to the Special Issue Biomimetic Peptides and Proteins)
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13 pages, 3853 KiB  
Review
Focused Overview of Mycobacterium tuberculosis VapBC Toxin–Antitoxin Systems Regarding Their Structural and Functional Aspects: Including Insights on Biomimetic Peptides
by Sung-Min Kang
Biomimetics 2023, 8(5), 412; https://doi.org/10.3390/biomimetics8050412 - 6 Sep 2023
Cited by 1 | Viewed by 1460
Abstract
Tuberculosis, caused by Mycobacterium tuberculosis, is a lethal infectious disease of significant public health concern. The rise of multidrug-resistant and drug-tolerant strains has necessitated novel approaches to combat the disease. Toxin–antitoxin (TA) systems, key players in bacterial adaptive responses, are prevalent in [...] Read more.
Tuberculosis, caused by Mycobacterium tuberculosis, is a lethal infectious disease of significant public health concern. The rise of multidrug-resistant and drug-tolerant strains has necessitated novel approaches to combat the disease. Toxin–antitoxin (TA) systems, key players in bacterial adaptive responses, are prevalent in prokaryotic genomes and have been linked to tuberculosis. The genome of M. tuberculosis strains harbors an unusually high number of TA systems, prompting questions about their biological roles. The VapBC family, a representative type II TA system, is characterized by the VapC toxin, featuring a PilT N-terminal domain with nuclease activity. Its counterpart, VapB, functions as an antitoxin, inhibiting VapC’s activity. Additionally, we explore peptide mimics designed to replicate protein helical structures in this review. Investigating these synthetic peptides offers fresh insights into molecular interactions, potentially leading to therapeutic applications. These synthetic peptides show promise as versatile tools for modulating cellular processes and protein–protein interactions. We examine the rational design strategies employed to mimic helical motifs, their biophysical properties, and potential applications in drug development and bioengineering. This review aims to provide an in-depth understanding of TA systems by introducing known complex structures, with a focus on both structural aspects and functional and molecular details associated with each system. Full article
(This article belongs to the Special Issue Biomimetic Peptides and Proteins)
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