scholarly journals Cross-Linked Self-Assembling Peptides and Their Post-Assembly Functionalization via One-Pot and In Situ Gelation System

2020 ◽  
Vol 21 (12) ◽  
pp. 4261
Author(s):  
Raffaele Pugliese ◽  
Fabrizio Gelain
Keyword(s):  
Mechanical Properties ◽  
Self Assembly ◽  
Self Healing ◽  
One Pot ◽  
Self Assembling ◽  
In Situ Gelation ◽  
Wide Range ◽  
Peptide Hydrogels ◽  
Peptide Hydrogel

Supramolecular nanostructures formed through peptide self-assembly can have a wide range of applications in the biomedical landscape. However, they often lose biomechanical properties at low mechanical stress due to the non-covalent interactions working in the self-assembling process. Herein, we report the design of cross-linked self-assembling peptide hydrogels using a one-pot in situ gelation system, based on 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide/N-hydroxysulfosuccinimide (EDC/sulfo–NHS) coupling, to tune its biomechanics. EDC/sulfo–NHS coupling led to limited changes in storage modulus (from 0.9 to 2 kPa), but it significantly increased both the strain (from 6% to 60%) and failure stress (from 19 to 35 Pa) of peptide hydrogel without impairing the spontaneous formation of β-sheet-containing nano-filaments. Furthermore, EDC/sulfo–NHS cross-linking bestowed self-healing and thixotropic properties to the peptide hydrogel. Lastly, we demonstrated that this strategy can be used to incorporate bioactive functional motifs after self-assembly on pre-formed nanostructures by functionalizing an Ac-LDLKLDLKLDLK-CONH2 (LDLK12) self-assembling peptide with the phage display-derived KLPGWSG peptide involved in the modulation of neural stem cell proliferation and differentiation. The incorporation of a functional motif did not alter the peptide’s secondary structure and its mechanical properties. The work reported here offers new tools to both fine tune the mechanical properties of and tailor the biomimetic properties of self-assembling peptide hydrogels while retaining their nanostructures, which is useful for tissue engineering and regenerative medicine applications.

scholarly journals In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245548
Author(s):  
Enrico Zurlo ◽  
Pravin Kumar ◽  
Georg Meisl ◽  
Alexander J. Dear ◽  
Dipro Mondal ◽  
...  
Keyword(s):  
Self Assembly ◽  
Large Population ◽  
Paramagnetic Resonance ◽  
Kinetic Measurements ◽  
Toxic Species ◽  
Self Assembling ◽  
Wide Range ◽  
Electron Paramagnetic

Knowledge of the mechanisms of assembly of amyloid proteins into aggregates is of central importance in building an understanding of neurodegenerative disease. Given that oligomeric intermediates formed during the aggregation reaction are believed to be the major toxic species, methods to track such intermediates are clearly needed. Here we present a method, electron paramagnetic resonance (EPR), by which the amount of intermediates can be measured over the course of the aggregation, directly in the reacting solution, without the need for separation. We use this approach to investigate the aggregation of α-synuclein (αS), a synaptic protein implicated in Parkinson’s disease and find a large population of oligomeric species. Our results show that these are primary oligomers, formed directly from monomeric species, rather than oligomers formed by secondary nucleation processes, and that they are short-lived, the majority of them dissociates rather than converts to fibrils. As demonstrated here, EPR offers the means to detect such short-lived intermediate species directly in situ. As it relies only on the change in size of the detected species, it will be applicable to a wide range of self-assembling systems, making accessible the kinetics of intermediates and thus allowing the determination of their rates of formation and conversion, key processes in the self-assembly reaction.

scholarly journals Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition

2018 ◽  
Vol 5 (3) ◽  
pp. 171562 ◽  
Author(s):  
Franziska Koch ◽  
Michael Müller ◽  
Finja König ◽  
Nina Meyer ◽  
Jasmin Gattlen ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Mechanical Characteristics ◽  
Network Formation ◽  
The Self ◽  
Peptide Sequence ◽  
Beta Sheet ◽  
Self Assembling ◽  
Buffer Composition ◽  
Peptide Hydrogels ◽  
Peptide Hydrogel

Self-assembling peptide hydrogels can be modified regarding their biodegradability, their chemical and mechanical properties and their nanofibrillar structure. Thus, self-assembling peptide hydrogels might be suitable scaffolds for regenerative therapies and tissue engineering. Owing to the use of various peptide concentrations and buffer compositions, the self-assembling peptide hydrogels might be influenced regarding their mechanical characteristics. Therefore, the mechanical properties and stability of a set of self-assembling peptide hydrogels, consisting of 11 amino acids, made from four beta sheet self-assembling peptides in various peptide concentrations and buffer compositions were studied. The formed self-assembling peptide hydrogels exhibited stiffnesses ranging from 0.6 to 205 kPa. The hydrogel stiffness was mostly affected by peptide sequence followed by peptide concentration and buffer composition. All self-assembling peptide hydrogels examined provided a nanofibrillar network formation. A maximum self-assembling peptide hydrogel dissolution of 20% was observed for different buffer solutions after 7 days. The stability regarding enzymatic and bacterial digestion showed less degradation in comparison to the self-assembling peptide hydrogel dissolution rate in buffer. The tested set of self-assembling peptide hydrogels were able to form stable scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are suitable for a regenerative therapy.

Factors Affecting Molecular Self-Assembly and Its Mechanism

2012 ◽  
Vol 9 (1) ◽  
pp. 43 ◽  
Author(s):  
Hueyling Tan
Keyword(s):  
Self Assembly ◽  
Building Blocks ◽  
Molecular Engineering ◽  
Molecular Structures ◽  
Polymer Science ◽  
New Approach ◽  
Factors Affecting ◽  
Dna Structures ◽  
Self Assembling ◽  
Wide Range

Molecular self-assembly is ubiquitous in nature and has emerged as a new approach to produce new materials in chemistry, engineering, nanotechnology, polymer science and materials. Molecular self-assembly has been attracting increasing interest from the scientific community in recent years due to its importance in understanding biology and a variety of diseases at the molecular level. In the last few years, considerable advances have been made in the use ofpeptides as building blocks to produce biological materials for wide range of applications, including fabricating novel supra-molecular structures and scaffolding for tissue repair. The study ofbiological self-assembly systems represents a significant advancement in molecular engineering and is a rapidly growing scientific and engineering field that crosses the boundaries ofexisting disciplines. Many self-assembling systems are rangefrom bi- andtri-block copolymers to DNA structures as well as simple and complex proteins andpeptides. The ultimate goal is to harness molecular self-assembly such that design andcontrol ofbottom-up processes is achieved thereby enabling exploitation of structures developed at the meso- and macro-scopic scale for the purposes oflife and non-life science applications. Such aspirations can be achievedthrough understanding thefundamental principles behind the selforganisation and self-synthesis processes exhibited by biological systems.

Indium Bromide-catalyzed Unprecedented Hydrogenolysis: A Novel One-Pot Synthesis of Per-O-Acetylated β-carboxymethyl O and S-glycosides

2020 ◽  
Vol 24 (8) ◽  
pp. 900-908
Author(s):  
Ram Naresh Yadav ◽  
Amrendra K Singh ◽  
Bimal Banik
Keyword(s):  
Asymmetric Synthesis ◽  
Chiral Auxiliary ◽  
Bioactive Molecules ◽  
One Pot ◽  
Enantiomerically Pure ◽  
Stereoselective Glycosylation ◽  
One Pot Synthesis ◽  
Wide Range

Numerous O (oxa)- and S (thia)-glycosyl esters and their analogous glycosyl acids have been accomplished through stereoselective glycosylation of various peracetylated bromo sugar with benzyl glycolate using InBr3 as a glycosyl promotor followed by in situ hydrogenolysis of resulting glycosyl ester. A tandem glycosylating and hydrogenolytic activity of InBr3 has been successfully investigated in a one-pot procedure. The resulting synthetically valuable and virtually unexplored class of β-CMGL (glycosyl acids) could serve as an excellent potential chiral auxiliary in the asymmetric synthesis of a wide range of enantiomerically pure medicinally prevalent β-lactams and other bioactive molecules of diverse medicinal interest.

scholarly journals Nanostructure, Self-Assembly, Mechanical Properties, and Antioxidant Activity of a Lupin-Derived Peptide Hydrogel

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 294
Author(s):  
Raffaele Pugliese ◽  
Anna Arnoldi ◽  
Carmen Lammi
Keyword(s):  
Mechanical Properties ◽  
Antioxidant Activity ◽  
Self Assembly ◽  
Antioxidant Activities ◽  
Functional Materials ◽  
Cd Spectroscopy ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
New Research ◽  
Peptide Hydrogel

Naturally occurring food peptides are frequently used in the life sciences due to their beneficial effects through their impact on specific biochemical pathways. Furthermore, they are often leveraged for applications in areas as diverse as bioengineering, medicine, agriculture, and even fashion. However, progress toward understanding their self-assembling properties as functional materials are often hindered by their long aromatic and charged residue-enriched sequences encrypted in the parent protein sequence. In this study, we elucidate the nanostructure and the hierarchical self-assembly propensity of a lupin-derived peptide which belongs to the α-conglutin (11S globulin, legumin-like protein), with a straightforward N-terminal biotinylated oligoglycine tag-based methodology for controlling the nanostructures, biomechanics, and biological features. Extensive characterization was performed via Circular Dichroism (CD) spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR), rheological measurements, and Atomic Force Microscopy (AFM) analyses. By using the biotin tag, we obtained a thixotropic lupin-derived peptide hydrogel (named BT13) with tunable mechanical properties (from 2 to 11 kPa), without impairing its spontaneous formation of β-sheet secondary structures. Lastly, we demonstrated that this hydrogel has antioxidant activity. Altogether, our findings address multiple challenges associated with the development of naturally occurring food peptide-based hydrogels, offering a new tool to both fine tune the mechanical properties and tailor the antioxidant activities, providing new research directions across food chemistry, biochemistry, and bioengineering.

Tandem Molecular Self-assembly for Selective Lung Cancer Therapy with Two Orders of Magnitude Increase in Efficiency

Nanoscale ◽  
2021 ◽  
Author(s):  
Debin Zheng ◽  
Jingfei Liu ◽  
Yinghao Ding ◽  
Limin Xie ◽  
Yingying Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Self Assembly ◽  
Therapeutic Efficacy ◽  
Self Assembling ◽  
Lung Cancer Therapy ◽  
Magnitude Increase

In situ self-assembling of prodrug molecules into nanomedicine can elevate the therapeutic efficacy of anticancer medications by enhancing the targeting and enrichment of anticancer drugs at tumor sites. However, the...

scholarly journals Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Luo ◽  
Yujuan Gao ◽  
Zhongyu Duan ◽  
Yu Yi ◽  
Hao Wang
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
Recent Progress ◽  
Assembly Systems ◽  
Targeted Cancer Therapy ◽  
Cancer Treatments ◽  
Self Assembling ◽  
Stimuli Response

Mitochondria are well known to serve as the powerhouse for cells and also the initiator for some vital signaling pathways. A variety of diseases are discovered to be associated with the abnormalities of mitochondria, including cancers. Thus, targeting mitochondria and their metabolisms are recognized to be promising for cancer therapy. In recent years, great efforts have been devoted to developing mitochondria-targeted pharmaceuticals, including small molecular drugs, peptides, proteins, and genes, with several molecular drugs and peptides enrolled in clinical trials. Along with the advances of nanotechnology, self-assembled peptide-nanomaterials that integrate the biomarker-targeting, stimuli-response, self-assembly, and therapeutic effect, have been attracted increasing interest in the fields of biotechnology and nanomedicine. Particularly, in situ mitochondria-targeted self-assembling peptides that can assemble on the surface or inside mitochondria have opened another dimension for the mitochondria-targeted cancer therapy. Here, we highlight the recent progress of mitochondria-targeted peptide-nanomaterials, especially those in situ self-assembly systems in mitochondria, and their applications in cancer treatments.

Molybdenum-Mediated One-Pot Synthesis of Pyrazoles from Isoxazoles

Synthesis ◽  
2019 ◽  
Vol 51 (20) ◽  
pp. 3796-3804 ◽  
Author(s):  
Marine Rey ◽  
Stéphane Beaumont
Keyword(s):  
Bond Cleavage ◽  
Direct Synthesis ◽  
Molybdenum Complex ◽  
One Pot ◽  
One Pot Synthesis ◽  
Wide Range ◽  
Hydrolysis Of ◽  
Substituted Pyrazoles

A one-pot approach for the direct synthesis of substituted pyrazoles from isoxazoles is reported. The process involves isoxazole N–O bond cleavage mediated by a molybdenum complex, in situ hydrolysis of the resulting β-amino enone to the corresponding 1,3-diketone, followed by pyrazole formation in the presence of hydrazine or substituted hydrazine. Good to excellent yields and regioselectivities are obtained with nonsymmetric isoxazoles. By using readily available starting materials, a wide range of substituted pyrazoles may be synthesized by this method.

Ordered mesoporous crystalline aluminas from self-assembly of ABC triblock terpolymer–butanol–alumina sols

RSC Advances ◽  
2015 ◽  
Vol 5 (61) ◽  
pp. 49287-49294 ◽  
Author(s):  
Kwan Wee Tan ◽  
Hiroaki Sai ◽  
Spencer W. Robbins ◽  
Jörg G. Werner ◽  
Tobias N. Hoheisel ◽  
...  
Keyword(s):  
Self Assembly ◽  
One Pot ◽  
Structure Directing Agent ◽  
One Pot Synthesis ◽  
Ordered Mesoporous

One-pot synthesis of periodically mesostructured γ-alumina using an ABC triblock terpolymer as structure-directing agent and in situ derived rigid carbon scaffold.

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