Rational Design of Programmable Monodisperse Semi-Synthetic Protein Nanomaterials Containing Engineered Disulfide Functionality

Mapping Intimacies ◽

10.1101/2021.02.05.430015 ◽

2021 ◽

Author(s):

Pavankumar Janardhan Bhandari ◽

Britto S Sandanaraj

Keyword(s):

Nucleic Acid ◽

Disulfide Bond ◽

Rational Design ◽

Inorganic Nanoparticles ◽

Stimuli Responsive ◽

Protein Assemblies ◽

Intelligent Materials ◽

Synthetic Protein ◽

Responsive Behavior ◽

Reversible Nature

AbstractThe reversible nature of disulfide functionality has been exploited to design intelligent materials such as nanocapsules, micelles, vesicles, inorganic nanoparticles, peptide and nucleic acid nanodevices. However, to our knowledge, there are no reports on design of semi-synthetic protein assemblies containing an engineered disulfide bond. Towards that end, herein, we disclose a new chemical methodology for the construction redox-sensitive protein assemblies using monodisperse facially amphiphilic protein-dendron bioconjugates. The disulfide functionality is strategically placed between the dendron and protein domains. The custom designed bioconjugates self-assembled into nanoscopic objects of a defined size dictated by the nature of dendron domain. The stimuli-responsive behavior of the protein assemblies is demonstrated using a suitable redox trigger.

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Constructing synthetic-protein assemblies from de novo designed 310 helices

10.1101/2021.12.11.471898 ◽

2021 ◽

Author(s):

Prasun Kumar ◽

Neil G. Paterson ◽

Jonathan Clayden ◽

Derek N. Woolfson

Keyword(s):

Rational Design ◽

De Novo ◽

Protein Structures ◽

Water Soluble ◽

Design Solution ◽

Protein Assemblies ◽

Synthetic Protein ◽

Hydrophobic Cores ◽

Α Helix ◽

Helical Folding

Compared with the iconic α helix, 310 helices occur much less frequently in protein structures. The different 310-helical parameters lead to energetically less favourable internal energies, and a reduced tendency to pack into defined higher-order structures. Consequently, in natural proteins, 310 helices rarely extend past 6 residues, and do not form regular supersecondary, tertiary, or quaternary interactions. Here, we show that despite their absence in nature, synthetic protein-like assemblies can be built from 310 helices. We report the rational design, solution-phase characterisation, and an X-ray crystal structure for water-soluble bundles of 310 helices with consolidated hydrophobic cores. The design uses 6-residue repeats informed by analysing natural 310 helices, and incorporates aminoisobutyric acid residues. Design iterations reveal a tipping point between α-helical and 310-helical folding, and identify features required for stabilising assemblies in this unexplored region of protein-structure space.

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Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

Physical Chemistry Chemical Physics ◽

10.1039/d0cp05759b ◽

2021 ◽

Vol 23 (1) ◽

pp. 219-228

Author(s):

Nabanita Saikia ◽

Mohamed Taha ◽

Ravindra Pandey

Keyword(s):

Nucleic Acid ◽

Boron Nitride ◽

Nucleic Acids ◽

Dynamic Stability ◽

Peptide Nucleic Acid ◽

Rational Design ◽

Peptide Nucleic Acids ◽

Boron Nitride Nanotubes ◽

Molecular Hybrids ◽

Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

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Synthesis and pH-stimuli responsive research of gemini amine-oxide surfactants containing amides

RSC Advances ◽

10.1039/d0ra07363f ◽

2020 ◽

Vol 10 (72) ◽

pp. 44387-44396

Author(s):

Hanyu Chen ◽

Duojiao Fu ◽

Xiqin Zhou ◽

Hongqin Liu ◽

Baocai Xu

Keyword(s):

Aqueous Solution ◽

Amine Oxide ◽

Stimuli Responsive ◽

Responsive Behavior

The series of gemini amine-oxide surfactants with the formula CnH2n+1CONH(CH2)2N+O–(CH3)–(CH2)3–(CH3)N+O– (CH2)2NHCOCnH2n+1 (n = 11, 13, 15, and 17) have been synthesized, and their pH-stimuli responsive behavior in aqueous solution has been studied.

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The Length of Disulfide Bond-Containing Linkages Impacts the Oral Absorption and Antitumor Activity of Paclitaxel Prodrugs-Loaded Nanoemulsions

Nanoscale ◽

10.1039/d1nr01359a ◽

2021 ◽

Author(s):

Yanlin Gao ◽

Shiyi Zuo ◽

Lingxiao Li ◽

Tian Liu ◽

Fudan Dong ◽

...

Keyword(s):

Antitumor Activity ◽

Oral Administration ◽

Disulfide Bond ◽

Rational Design ◽

Oral Absorption ◽

Oral Paclitaxel

Rational design of oral paclitaxel (PTX) preparations is still a challenge. Many studies focus on developing PTX-loaded nanoemulsions (NEs) for oral administration. Unfortunately, PTX has poor affinity with the commonly...

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Microgels and Nanoparticles: Where Micro and Nano Go Hand in Hand

Zeitschrift für Physikalische Chemie ◽

10.1515/zpch-2014-0578 ◽

2015 ◽

Vol 229 (1-2) ◽

Author(s):

Beatriz H. Juarez ◽

Luis M. Liz-Marzán

Keyword(s):

Magnetic Nanoparticles ◽

Optical Tweezers ◽

Hybrid System ◽

Inorganic Nanoparticles ◽

Stimuli Responsive ◽

Single Particles ◽

Nanoscale Systems ◽

Different Types ◽

Potential Applications ◽

Very High

AbstractThe integration of different types of materials in a single hybrid system allows the combination of multiple functionalities, which can even be used in conjunction with each other. This strategy has been exploited in nanoscale systems for the creation of so-called smart nanomaterials. Within this category, the combination of inorganic nanoparticles with stimuli-responsive microgels is of very high interest because of the wide variety of potential applications. We present here a short overview of this type of materials in which the nano- and micro-scales get nicely integrated, with a great potential to expand the range of technological applications. We focus mainly on the integration of metal nanoparticles, either by themselves or in combination with semiconductor and magnetic nanoparticles. Various examples of the synergic properties that can be obtained are described, as well as the possibility to extract useful information when optical tweezers are used to manipulate single particles. We expect that this review will stimulate additional research in this field.

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Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering

Applied Sciences ◽

10.3390/app112311369 ◽

2021 ◽

Vol 11 (23) ◽

pp. 11369

Author(s):

Ashni Arun ◽

Pratyusha Malrautu ◽

Anindita Laha ◽

Hongrong Luo ◽

Seeram Ramakrishna

Keyword(s):

Drug Delivery ◽

Tissue Engineering ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Drug Solubility ◽

Stimuli Responsive ◽

Preparation Methods ◽

Nanoparticle Preparation ◽

Responsive Behavior ◽

Reduced Toxicity

The versatile natural polymer, collagen, has gained vast attention in biomedicine. Due to its biocompatibility, biodegradability, weak antigenicity, biomimetics and well-known safety profile, it is widely used as a drug, protein and gene carrier, and as a scaffold matrix in tissue engineering. Nanoparticles develop favorable chemical and physical properties such as increased drug half-life, improved hydrophobic drug solubility and controlled and targeted drug release. Their reduced toxicity, controllable characteristics of scaffolds and stimuli-responsive behavior make them suitable in regenerative medicine and tissue engineering. Collagen associates and absorbs nanoparticles leading to significant impacts on their biological functioning in any biofluid. This review will discuss collagen nanoparticle preparation methods and their applications and developments in drug delivery systems and tissue engineering.

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Methods for Evaluating the Stimuli-Responsive Delivery of Nucleic Acid and Gene Medicines

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.c17-00096 ◽

2017 ◽

Vol 65 (7) ◽

pp. 642-648 ◽

Cited By ~ 5

Author(s):

Shintaro Fumoto ◽

Koyo Nishida

Keyword(s):

Nucleic Acid ◽

Stimuli Responsive

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Molecular Dynamics Simulation and Kinetic Study of Fluoride Binding to V21C/V66C Myoglobin with a Cytoglobin-like Disulfide Bond

International Journal of Molecular Sciences ◽

10.3390/ijms21072512 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2512

Author(s):

Lu-Lu Yin ◽

Jia-Kun Xu ◽

Xiao-Juan Wang ◽

Shu-Qin Gao ◽

Ying-Wu Lin

Keyword(s):

Molecular Dynamics ◽

Disulfide Bond ◽

Rational Design ◽

Double Mutant ◽

Md Simulation ◽

Experimental Studies ◽

Heme Iron ◽

Dynamics Simulation ◽

Fluoride Ion ◽

Artificial Proteins

Protein design is able to create artificial proteins with advanced functions, and computer simulation plays a key role in guiding the rational design. In the absence of structural evidence for cytoglobin (Cgb) with an intramolecular disulfide bond, we recently designed a de novo disulfide bond in myoglobin (Mb) based on structural alignment (i.e., V21C/V66C Mb double mutant). To provide deep insight into the regulation role of the Cys21-Cys66 disulfide bond, we herein perform molecular dynamics (MD) simulation of the fluoride–protein complex by using a fluoride ion as a probe, which reveals detailed interactions of the fluoride ion in the heme distal pocket, involving both the distal His64 and water molecules. Moreover, we determined the kinetic parameters of fluoride binding to the double mutant. The results agree with the MD simulation and show that the formation of the Cys21-Cys66 disulfide bond facilitates both fluoride binding to and dissociating from the heme iron. Therefore, the combination of theoretical and experimental studies provides valuable information for understanding the structure and function of heme proteins, as regulated by a disulfide bond. This study is thus able to guide the rational design of artificial proteins with tunable functions in the future.

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