Labeling of Nanofiber-Forming Peptides by Site-Directed Bioconjugation: Effect of Spacer Length on Self-Assembly

2019 ◽  
Vol 16 (2) ◽  
pp. 319-325
Author(s):  
Alessandra Scelsi ◽  
Brigida Bochicchio ◽  
Antonietta Pepe

Background: The conjugation of small organic molecules to self-assembling peptides is a versatile tool to decorate nanostructures with original functionalities. Labeling with chromophores or fluorophores, for example, creates optically active fibers with potential interest in photonic devices. Aim and Objective: In this work, we present a rapid and effective labeling procedure for a self-assembling peptide able to form nanofibers. Rapid periodate oxidation of the N-terminal serine residue of the peptide and subsequent conjugation with dansyl moiety generated fluorophore-decorated peptides. Results: Three dansyl-conjugated self-assembling peptides with variable spacer-length were synthesized and characterized and the role of the size of the linker between fluorophore and peptide in self-assembling was investigated. Our results show that a short linker can alter the self-assembly in nanofibers of the peptide. Conclusions: Herein we report on an alternative strategy for creating functionalized nanofibrils, able to expand the toolkit of chemoselective bioconjugation strategies to be used in site-specific decoration of self-assembling peptides.

2020 ◽  
Vol 27 (9) ◽  
pp. 923-929
Author(s):  
Gaurav Pandey ◽  
Prem Prakash Das ◽  
Vibin Ramakrishnan

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.


2019 ◽  
Vol 4 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Ryan T. Shafranek ◽  
Joel D. Leger ◽  
Song Zhang ◽  
Munira Khalil ◽  
Xiaodan Gu ◽  
...  

Directed self-assembly in polymeric hydrogels allows tunability of thermal response and viscoelastic properties.


RSC Advances ◽  
2016 ◽  
Vol 6 (75) ◽  
pp. 71638-71651 ◽  
Author(s):  
Ankita Saini ◽  
K. R. Justin Thomas

The self-assembly of small organic molecules into molecular stacks plays a vital role in the construction of stable supramolecular structures.


2020 ◽  
Vol 21 (6) ◽  
pp. 2002 ◽  
Author(s):  
Darcy C. Engelhart ◽  
Priti Azad ◽  
Suwayda Ali ◽  
Jeffry C. Granados ◽  
Gabriel G. Haddad ◽  
...  

The SLC22 family of transporters is widely expressed, evolutionarily conserved, and plays a major role in regulating homeostasis by transporting small organic molecules such as metabolites, signaling molecules, and antioxidants. Analysis of transporters in fruit flies provides a simple yet orthologous platform to study the endogenous function of drug transporters in vivo. Evolutionary analysis of Drosophila melanogaster putative SLC22 orthologs reveals that, while many of the 25 SLC22 fruit fly orthologs do not fall within previously established SLC22 subclades, at least four members appear orthologous to mammalian SLC22 members (SLC22A16:CG6356, SLC22A15:CG7458, CG7442 and SLC22A18:CG3168). We functionally evaluated the role of SLC22 transporters in Drosophila melanogaster by knocking down 14 of these genes. Three putative SLC22 ortholog knockdowns—CG3168, CG6356, and CG7442/SLC22A—did not undergo eclosion and were lethal at the pupa stage, indicating the developmental importance of these genes. Additionally, knocking down four SLC22 members increased resistance to oxidative stress via paraquat testing (CG4630: p < 0.05, CG6006: p < 0.05, CG6126: p < 0.01 and CG16727: p < 0.05). Consistent with recent evidence that SLC22 is central to a Remote Sensing and Signaling Network (RSSN) involved in signaling and metabolism, these phenotypes support a key role for SLC22 in handling reactive oxygen species.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Chun Yin Jerry Lau ◽  
Federico Fontana ◽  
Laurens D. B. Mandemaker ◽  
Dennie Wezendonk ◽  
Benjamin Vermeer ◽  
...  

AbstractSelf-assembling peptides are an exemplary class of supramolecular biomaterials of broad biomedical utility. Mechanistic studies on the peptide self-assembly demonstrated the importance of the oligomeric intermediates towards the properties of the supramolecular biomaterials being formed. In this study, we demonstrate how the overall yield of the supramolecular assemblies are moderated through subtle molecular changes in the peptide monomers. This strategy is exemplified with a set of surfactant-like peptides (SLPs) with different β-sheet propensities and charged residues flanking the aggregation domains. By integrating different techniques, we show that these molecular changes can alter both the nucleation propensity of the oligomeric intermediates and the thermodynamic stability of the fibril structures. We demonstrate that the amount of assembled nanofibers are critically defined by the oligomeric nucleation propensities. Our findings offer guidance on designing self-assembling peptides for different biomedical applications, as well as insights into the role of protein gatekeeper sequences in preventing amyloidosis.


2006 ◽  
Vol 09 (01n02) ◽  
pp. 1-29 ◽  
Author(s):  
RUDOLF M. FÜCHSLIN ◽  
THOMAS MAEKE ◽  
UWE TANGEN ◽  
JOHN S. McCASKILL

We propose that genetic encoding of self-assembling components greatly enhances the evolution of complex systems and provides an efficient platform for inductive generalization, i.e. the inductive derivation of a solution to a problem with a potentially infinite number of instances from a limited set of test examples. We exemplify this in simulations by evolving scalable circuitry for several problems. One of them, digital multiplication, has been intensively studied in recent years, where hitherto the evolutionary design of only specific small multipliers was achieved. The fact that this and other problems can be solved in full generality employing self-assembly sheds light on the evolutionary role of self-assembly in biology and is of relevance for the design of complex systems in nano- and bionanotechnology.


2017 ◽  
Vol 196 ◽  
pp. 305-316 ◽  
Author(s):  
Pengfei Duan ◽  
Deepak Asthana ◽  
Takuya Nakashima ◽  
Tsuyoshi Kawai ◽  
Nobuhiro Yanai ◽  
...  

Aggregation-induced photon upconversion (iPUC) based on a triplet–triplet annihilation (TTA) process is successfully developed via controlled self-assembly of donor–acceptor pairs in organogel nanoassemblies. Although segregation of donor from acceptor assemblies has been an outstanding problem in TTA-based UC and iPUC, we resolved this issue by modifying both the triplet donor and aggregation induced emission (AIE)-type acceptor with glutamate-based self-assembling moieties. These donors and acceptors co-assemble to form organogels without segregation. Interestingly, these donor–acceptor binary gels show upconversion at room temperature but the upconversion phenomena were lost upon dissolution of the gels on heating. The observed changes in TTA-UC emission were thermally reversible, reflecting the controlled assembly/disassembly of the binary molecular systems. The observed on/off ratio of UC emission was much higher than that of the aggregation-induced fluorescence of the acceptor, which highlights the important role of iPUC, i.e., multi-exciton TTA for photoluminescence switching. This work bridges iPUC and supramolecular chemistry and provides a new strategy for designing stimuli-responsive upconversion systems.


Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3112
Author(s):  
Jack Freeland ◽  
Lihua Zhang ◽  
Shih-Ting Wang ◽  
Mason Ruiz ◽  
Yong Wang

Due to the central role of DNA, its interactions with inorganic salts and small organic molecules are important. For example, such interactions play important roles in various fundamental cellular processes in living systems and are involved in many DNA-damage related diseases. Strategies to improve the sensitivity of existing techniques for studying DNA interactions with other molecules would be appreciated in situations where the interactions are too weak. Here we report our development and demonstration of bent DNA bows for amplifying, sensing, and detecting the interactions of 14 inorganic salts and small organic molecules with DNA. With the bent DNA bows, these interactions were easily visualized and quantified in gel electrophoresis, which were difficult to measure without bending. In addition, the strength of the interactions of DNA with the various salts/molecules were quantified using the modified Hill equation. This work highlights the amplification effects of the bending elastic energy stored in the DNA bows and the potential use of the DNA bows for quantitatively measuring DNA interactions with small molecules as simple economic methods; it may also pave the way for exploiting the bent DNA bows for other applications such as screening DNA-interacting molecules and drugs.


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