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Self-assembling peptide

Hongjian He, Jiaqing Wang, Huaimin Wang, Ning Zhou, Dongsik Yang, Douglas R Green, Bing Xu
Most of the reported mitochondria targeting molecules are lipophilic and cationic, which may become cytotoxic with accumulation. Here we show enzymatic cleavage of branched peptides that carry negative charges for targeting mitochondria. Conjugating a well-established protein tag (i.e., FLAG-tag) to self-assembling motifs affords the pre-cursors that form micelles. Enzymatic cleavage of the hydrophilic FLAG motif (DDDDK) by enterokinase (ENTK) turns the micelles to nanofibers. After being taken up by cells, the micelles, upon the action of intracellular ENTK, turns into nanofibers to locate mainly at mitochondria...
January 12, 2018: Journal of the American Chemical Society
Reza Motalleb, Eric J Berns, Piyush Patel, Julie Gold, Samuel I Stupp, H Georg Kuhn
Biomaterials hold great promise in helping the adult brain regenerate and rebuild after trauma. Peptide amphiphiles (PA) are highly versatile biomaterials, gelling and forming macromolecular structures when exposed to physiological levels of electrolytes. We are here reporting on the first ever in vivo use of self-assembling peptide amphiphile carrying a Tenascin-C signal (E2 Ten-C PA) for the re-direction of endogenous neuroblasts in the rodent brain. The PA forms highly aligned nanofibers, displaying the migratory sequence of Tenascin-C glycoprotein as epitope...
January 12, 2018: Journal of Tissue Engineering and Regenerative Medicine
Chi Zhang, Li-Han Liu, Wen-Xiu Qiu, Yao-Hui Zhang, Wen Song, Lu Zhang, Shi-Bo Wang, Xian-Zheng Zhang
Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P-glycoprotein (P-gp)-mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self-assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C16 -K(TPE)-GGGH-GFLGK-PEG8 , denoted as CTGP) with cathepsin B-responsive and cell membrane-targeting abilities can self-assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX)...
January 11, 2018: Small
Wei Du, Xiaomu Hu, Weichen Wei, Gaolin Liang
Most of the nano-drugs are pre-prepared by encapsulating or loading the drugs with nano-carriers (e.g., dendrimers, liposomes, micelles, and polymeric nanoparticles). However, besides the low bioavailability and fast excretion of the nano-drugs in vivo, nano-carriers often exhibit in vitro and in vivo cytotoxicity, oxidative stress, and inflammation. Self-assembly is a ubiquitous process in biology where it plays important roles and underlies the formation of a wide variety of complex biological structures...
January 9, 2018: Bioconjugate Chemistry
Xi Yu, Xingchun Gou, Peng Wu, Liang Han, Daofeng Tian, Fengyi Du, Zeming Chen, Fuyao Liu, Gang Deng, Ann T Chen, Chao Ma, Jun Liu, Sara M Hashmi, Xing Guo, Xiaolong Wang, Haitian Zhao, Xinran Liu, Xudong Zhu, Kevin Sheth, Qianxue Chen, Louzhen Fan, Jiangbing Zhou
Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self-assembly of three independent polypeptides based on pairwise coiled-coil dimerization...
January 8, 2018: Advanced Materials
Yesim Tugce Yaman, Öznur Akbal, Gulcin Bolat, Betul Bozdogan, Emir Baki Denkbas, Serdar Abaci
A novel diphenylalaninamid (FFA) based peptide nanoparticles (PNPs) modified pencil graphite electrodes (PGEs) for construction of electrochemical cytosensor was demonstrated for the first time in this study. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed the spherical nanostructure of the synthesized FFA based PNPs while attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectra provided information about the structure and conformation of proteins in their structure...
December 25, 2017: Biosensors & Bioelectronics
Fan Xu, Huihai Zhong, Ya Chang, Dongdong Li, Hongyue Jin, Meng Zhang, Huiyuan Wang, Chen Jiang, Youqing Shen, Yongzhuo Huang
Chemoresistance remains a formidable hurdle against cancer therapy. Seeking for novel therapy strategies is an urgent need for those who no longer benefit from chemotherapy. Chemoresistance is usually associated with the dysfunction of intrinsic apoptosis. Targeting extrinsic apoptosis via TRAIL signaling and the death receptors could be a potential solution to treat chemoresistant cancer. A highly biocompatible nano system for codelivery of the TRAIL DNA and the death receptor sensitizer monensin was developed, in which low-molecular-weight PEI (LMW-PEI) was crosslinked by the sulfhydryl cyclodextrin via disulfide bonds, and then bound with DNA, thus forming the bioreducible polyplex cores...
December 22, 2017: Biomaterials
Kei Ando, Shiro Imagama, Kazuyoshi Kobayashi, Kenyu Ito, Mikito Tsushima, Masayoshi Morozumi, Satoshi Tanaka, Masaaki Machino, Kyotaro Ota, Koji Nishida, Yoshihiro Nishida, Naoki Ishiguro
Spinal fusion and bone defect after injuries, removal of bone tumors, and infections need to be repaired by implantation. In an aging society, recovery from these procedures is often difficult. In this study, we found that injection of SPG-178 leads to expression of several bone marker genes and mineralization in vitro, and revealed a significantly higher degree of newly formed bone matrix with use of SPG-178 in vivo. MC3T3-E1 cells were used to evaluate osteoblast differentiation promoted by SPG-178. To analyze gene expression, total RNA was isolated from MC3T3-E1 cells cultured for 7 and 14 days with control medium or SPG-178 medium...
2018: PloS One
Nikola A Dudukovic, Benjamin C Hudson, Anant K Paravastu, Charles F Zukoski
Dipeptide derivative molecules can self-assemble into space-filling nanofiber networks at low volume fractions (<1%), allowing the formation of molecular gels with tunable mechanical properties. The self-assembly of dipeptide-based molecules is reminiscent of pathological amyloid fibril formation by naturally occurring polypeptides. Fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) is the most widely studied such molecule, but the thermodynamic and kinetic phenomena giving rise to Fmoc-FF gel formation remain poorly understood...
January 5, 2018: Nanoscale
Jai S Rudra, Arshad Khan, Tara M Clover, Janice J Endsley, Andrew Zloza, Jin Wang, Chinnaswamy Jagannath
Supramolecular peptide nanofibers are attractive for applications in vaccine development due to their ability to induce strong immune responses without added adjuvants or associated inflammation. Here, we report that self-assembling peptide nanofibers bearing CD4+ or CD8+ T cell epitopes are processed through mechanisms of autophagy in antigen-presenting cells (APCs). Using standard in vitro antigen presentation assays, we confirmed loss and gain of the adjuvant function using pharmacological modulators of autophagy and APCs deficient in multiple autophagy proteins...
December 31, 2017: ACS Omega
Hongchao Ma, Shuo Li, Yanhui Wei, Lei Jiang, Junbai Li
An azobenzene with a terminal formyl group, named as (4-[(3-Formyl-4-hydroxy)phenylazo]benzene (FHPAB)), was synthesized and used to manipulate the self-assembly of diphenylalanine (FF) molecules. Two-dimensional (2D) thin slices which are composed of ordered microspheres have been constructed through supramolecular self-assembly of FF and FHPAB. The FTIR and XPS results indicate that CN covalent bond between FF and FHPAB was generated. Hydrogen bonding and strong π-π interaction between the planar FF-HFPAB conjugates are the driving force to form the FF-HFPAB 2D thin slices...
December 22, 2017: Journal of Colloid and Interface Science
Christopher Poon, Manjima Sarkar, Eun Ji Chung
Atherosclerosis is a major contributor to cardiovascular disease, the leading cause of death worldwide, which claims 17.3 million lives annually. Atherosclerosis is also the leading cause of sudden death and myocardial infarction, instigated by unstable plaques that rupture and occlude the blood vessel without warning. Current imaging modalities cannot differentiate between stable and unstable plaques that rupture. Peptide amphiphiles micelles (PAMs) can overcome this drawback as they can be modified with a variety of targeting moieties that bind specifically to diseased tissue...
November 17, 2017: Journal of Visualized Experiments: JoVE
Tsutomu Sugihara, Masayasu Mie, Eiry Kobatake
Nanoparticles are small size-controlled particles from 1 to 100 nm diameters and characterized by their structure, base material and functional units displayed on their surfaces. In this study, protein-based nanoparticles composed of a hydrophobic elastin-like peptide unit, a hydrophilic aspartic acid-rich peptide unit and displaying antibody binding domains on their surfaces, were designed and genetically synthesized. The constituent fusion proteins, termed ELP-D-C, were found to exist in monomeric form (ELP-D-C/monomer) at low temperature...
December 25, 2017: Analytical Biochemistry
Akihiro J Matsuoka, Zafar A Sayed, Nicholas Stephanopoulos, Eric J Berns, Anil R Wadhwani, Zachery D Morrissey, Duncan M Chadly, Shun Kobayashi, Alexandra N Edelbrock, Tomoji Mashimo, Charles A Miller, Tammy L McGuire, Samuel I Stupp, John A Kessler
The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears...
2017: PloS One
Maria Paola Conte, Jugal Kishore Kishore Sahoo, Yousef M Abul-Haija, King Hang Aaron Lau, Rein V Ulijn
Combining (bio-)catalysis and molecular self-assembly provides an effective approach for the production and processing of self-assembled materials, by exploiting catalysis to direct the assembly kinetics and hence control the formation of ordered nanostructures. Applications of (bio-)catalytic self-assembly in biologically interfacing systems and in nanofabrication have recently been reported. Inspired by self-assembly in biological cells, efforts to confine catalysts on flat or patterned surfaces to exert spatial control over molecular gelator generation and nanostructure self-assembly have also emerged...
December 28, 2017: ACS Applied Materials & Interfaces
Andrew Boden, Mrinal Bhave, Peng-Yuan Wang, Snehal R Jadhav, Peter Kingshott
The ability of bacteria to form biofilms and the emergence of antibiotic-resistant strains has prompted the need to develop the next-generation of antibacterial coatings. Antimicrobial peptides (AMPs) are showing promise as molecules that can address these issues, especially if used when immobilized as a surface coating. We present a method that explores how surface patterns together with the selective immobilization of an AMP called PuroA (FPVTWRWWKWWKG-NH2) can be used to both kill bacteria, but also as a tool to study bacterial attachment mechanisms...
December 28, 2017: ACS Applied Materials & Interfaces
Fang-Fang Wu, Ying Zhou, Han Zhang, Ruo Yuan, Ya-Qin Chai
In this work, a luminol-centric biosensor was constructed for the ultrasensitive detection of tryptase (TPS) combining dissolved O2 as the endogenous coreactant and Au-Ag-Pt hetero-nanostructures (AAPHNs) as co-reaction accelerator. Dissolved O2 could rapidly generate superoxide anion radical (O2•-) with the catalysis of AAPHNs to in situ react with luminol anion radical (L•-) to generate excited-state species 3-aminophthalate (AP2-*) for emitting ECL signal, resulting in a remarkable "single on" state...
December 27, 2017: Analytical Chemistry
Yusuke Azuma, Thomas G W Edwardson, Naohiro Terasaka, Donald Hilvert
Protein cages have recently emerged as an important platform for nanotechnology development. Of the naturally existing protein cages, viruses are among the most efficient nanomachines, overcoming various barriers to achieve component replication and efficient self-assembly in complex biological milieu. We have designed an artificial system that can carry out the most basic steps of viral particle assembly in vivo. Our strategy is based on patchwork capsids formed from Aquifex aeolicus lumazine synthase and a circularly permuted variant with appended cationic peptides...
January 3, 2018: Journal of the American Chemical Society
Jie Zhan, Yanbin Cai, Shuangshuang He, Ling Wang, Zhimou Yang
We introduce in this study tandem molecular self-assembly of a peptide derivative (compound 1) that is controlled by a combination of enzymatic and chemical reactions. In PBS, compound 1 self-assembles first into nanoparticles by phosphatase and then into nanofibers by glutathione. Liver cancer cells exhibit higher concentrations of both phosphatase and GSH than normal cells. Therefore, the tandem self-assembly of 1 also occurs in liver cancer cell lines HepG2 and QGY7703, in which compound 1 first forms nanoparticles around the cells and then forms nanofibers inside the cells...
December 24, 2017: Angewandte Chemie
Johanna M Galloway, Laura Senior, Jordan M Fletcher, Joseph L Beesley, Lorna R Hodgson, Robert L Harniman, Judith M Mantell, Jennifer Coombs, Guto G Rhys, Wei-Feng Xue, Majid Mosayebi, Noah Linden, Tanniemola B Liverpool, Paul Curnow, Paul Verkade, Derek N Woolfson
Understanding how molecules in self-assembled soft-matter nanostructures are organized is essential for improving the design of next-generation nanomaterials. Imaging these assemblies can be challenging and usually requires processing, e.g. staining or embedding, which can damage or obscure features. An alternative is to use bioinspired mineralization, mimicking how certain organisms use biomolecules to template mineral formation. Previously, we have reported the design and characterization of Self-Assembled peptide caGEs (SAGEs) formed from de novo peptide building blocks...
December 25, 2017: ACS Nano
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