tropoelastin allergantropoelastin allergan

Allergan's Medical Aesthetics business - a comprehensive portfolio of facial aesthetics, body contouring and plastic and regenerative medicine products - is expected to grow at an 8-10 percent. Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: clues to the evolutionary history of elastins. Synthesis and structural studies of a pentapeptide sequence of elastin. doi: 10.1161/circimaging.117.007303, Prhashanna, A., Taylor, P. A., Qin, J., Kiick, K. L., and Jayaraman, A. Proline-poor hydrophobic domains modulate the assembly and material properties of polymeric elastin. doi: 10.1073/pnas.1111615108, Yeo, G. C., Baldock, C., Wise, S. G., and Weiss, A. S. (2017). 29, 152159. (2017). Elastagen is an exciting clinical-stage company with an advanced tissue repair platform based on tropoelastin. doi: 10.1074/jbc.M107920200, Tu, Y., and Weiss, A. S. (2010). Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated . More recently, the computational model of tropoelastin has been leveraged to characterize higher-order structures and probe self-assembly (Tarakanova et al., 2019a). Modeling utilizing tropoelastin derivatives has demonstrated that structural compaction into both coils and globules occurs above the transition temperature of self-assembly, which may assist in explaining the anisotropic nature of mature elastin (Baul et al., 2020). Tropoelastin: a versatile, bioactive assembly module - PubMed Tropoelastin is a spring-like molecule that is extremely extensible prior to cross-linking. Int. We are very interested in the blend of biochemistry and cell biology, as well as the tissue engineering and regenerative medicine opportunities provided by this amazing elastic protein. doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. It has become increasingly evident that tropoelastins sequence, structure and subsequent functionality are in a delicate balance; thus, perturbations to tropoelastins sequence can have far-reaching consequences for self-assembly and the resultant architecture of elastic fibers. J. Biol. I thank my team at the University of Sydney and greatly look forward to seeing our science commercialized by Allergan.. Solving tropoelastins global structure (Baldock et al., 2011) allowed for 3D mapping on tropoelastin of the approximate locations of domains 10, 19, and 25, which were the first unequivocally cross-linked domains to be discovered (Brown-Augsburger et al., 1995). Latent TGF- binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Water structure and elastin-like peptide aggregation. It is likely that, as a general rule, integrin binding to tropoelastin is mediated via GAGs, which is facilitated by the repetition of tropoelastins primary sequence and the surface exposure of positively charged similar domains (Lee et al., 2017; Bochicchio et al., 2021). This content is for members only. The ELN gene provides instructions for making a protein called tropoelastin. (2017). Engineering a highly elastic human protein-based sealant for surgical applications. doi: 10.1002/bip.23007, Miao, M., Stahl, R. J., Petersen, L. F., Reintsch, W. E., Davis, E. C., and Keeley, F. W. (2009). Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global biopharmaceutical company. U.S.A. 112, E4408E4415. Cell Biol. A novel cell adhesion region in tropoelastin mediates attachment to integrin alphaVbeta5. 10, 15321541. Biol. Nature 437, 9991002. Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. Sci. The ability to stretch and recoil arises from the biochemical properties of elastins monomer, tropoelastin (discussed below). Elastic fibers are present in the extracellular matrix (ECM) of vertebrate tissues, such as the skin, lungs, cardiovascular system, cartilage, and tendons. Mater. More surprisingly, tropoelastins cross-linking domains are also capable of similar transitions between ordered and disordered structures. The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). J. Hum. Reichheld, S. E., Muiznieks, L. D., Huynh, Q., Wang, N., Ing, C., Miao, M., et al. Thus, at lower temperatures, the water surrounding these domains forms ordered, clathrate-like shells that prevent aggregation until the appropriate temperature is reached (Wu and Weiss, 1999; Miao et al., 2003; Dandurand et al., 2015). Of most importance, the inability to acquire large quantities of pure tropoelastin historically presented a significant obstacle to experimentally characterizing its structure. doi: 10.1074/jbc.M609505200, Dyksterhuis, L. B., Baldock, C., Lammie, D., Wess, T. J., and Weiss, A. S. (2007). Chem. doi: 10.1021/bi00835a021, Gray, W. R., Sandberg, L. B., and Foster, J. FEBS J. However, higher resolution data were required to map out its elusive properties and performance within a hierarchical assembly (Tarakanova et al., 2018; Ozsvar et al., 2019). Tropoelastin is a flexible molecule that retains its canonical shape. Tropoelastin spherules assemble at the cell surface before deposition onto the microfibrillar scaffold in cell culture systems at physiological temperature (Kozel et al., 2006). Tropoelastin was revealed to be an asymmetric molecule with distinct N- and C-terminal regions that are respectively referred to as the head and foot of the molecule. doi: 10.1016/j.micron.2009.11.003, Urban, Z., Hucthagowder, V., Schrmann, N., Todorovic, V., Zilberberg, L., Choi, J., et al. The smallest amino acid, glycine is known to promote flexibility within local structures due to lack of steric hindrance, whereas prolines restrictive sidechain inhibits conformational sampling and disrupts the formation of prolonged secondary structures (Roberts et al., 2015). In addition to the RKRK sequence, domain 36 contains tropoelastins sole two cysteines and only disulfide bond. 260, 32553258. Coacervation characteristics of recombinant human tropoelastin. Elastin is the major component of elastic fibers, which are a major component of the tissue that supports the body's joints . 9:eaai7466. The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. Parameter, Testing, and Method. Thus, computational approaches can be considered as important means to complement wet bench experiments. 11 Articles, This article is part of the Research Topic, Tropoelastin-Cell Receptor Interactions and Implications for Assembly, https://doi.org/10.3389/fbioe.2021.643110, Creative Commons Attribution License (CC BY). Another region of note is domain 36, which contains lysines but does not participate in cross-linking (Hedtke et al., 2019). HS, which is present on cell surface proteoglycans (syndecans and glypicans), interacts strongly with tropoelastin (Cain et al., 2005). Tropoelastin: a novel marker for plaque progression and instability. Combinations of these two amino acids result in domains that undergo rapid conformational sampling (Rauscher and Pomes, 2017), which, if perturbed toward a conformation that gravitate toward stability, will assemble into highly ordered amyloid-like fibrils that are not elastomeric (Rauscher et al., 2006; Roberts et al., 2015). 3, 4 Elastin has a very low rate of turnover, so it . The most commonly investigated isoform contains domain 26A and lacks domain 22, and is predominantly found in elastic tissues (Indik et al., 1987; Vrhovski et al., 1997). 396, 870873. 293, 1510715119. Cardiovasc. Commun. (1995). 87, 18281834. doi: 10.1016/s0021-9258(19)43030-5, Dandurand, J., Samouillan, V., Lacabanne, C., Pepe, A., and Bochicchio, B. Lab. 85, 593605. Implications for tissue specificity and durability of elastic tissue. This product is generally used in vitro as a substrate scaffold to enhance cell attachment, adherence and proliferation. doi: 10.1016/s0945-053x(03)00014-3, Vrhovski, B., Jensen, S., and Weiss, A. S. (1997). Tropoelastin is the soluble precursor of elastin that is secreted as a 60-70-kDa monomer by elastogenic cells such as fibroblasts, lung alveolar cells, chondrocytes, and vascular SMCs [16]. J. Biochem. J. Biol. (2006). doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. FASEB J. Transl. A new amino acid from hydrolysates of elastin. Biosynthesis and nature of elastin structures. doi: 10.1002/bip.360291403, Luo, P., and Baldwin, R. L. (1997). Chem. 25, 10231029. 28, 379382. AW is the Scientific Founder of Elastagen Pty. Chem. Adv. Fluor: Q4 Earnings Snapshot. Proc. Comparative genomics of elastin: sequence analysis of a highly repetitive protein. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). 79, 277284. doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. Elastogenic cells, such as fibroblasts (Mecham et al., 1985) and smooth muscle cells (Narayanan et al., 1976), synthesize and secrete tropoelastin. The narrow specificity to v3 and 53 may also be beneficial compared with other ECM adhesion molecules such as fibronectin (which can adhere to up to 20 types of integrin) which may compete with and modulate binding to tropoelastin, and deliver opposing effects on cell proliferation. J. Exp. 10, 441454. Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. Biol. Bonnans, C., Chou, J., and Werb, Z. Allergan's Medical Aesthetics business - a comprehensive portfolio of facial aesthetics, body contouring and plastic and regenerative medicine products - is expected to grow at an 8-10 percent CAGR from 2017 to 2025. Biopolymers 107:e23007. Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie . Biophys. Biochimie 86, 173178. Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. 1862, 324334. Computational approaches have gained popularity in recent decades as their methodologies have been refined to provide accurate atomistic scale insights into molecular structure and movement (Tarakanova et al., 2018). Invest. Molecular modeling of protein materials: case study of elastin. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. Ltd., which was sold to Allergan, now a division of AbbVie. (2012). Cell. Chem. Cell Biol. doi: 10.1002/jcp.20546, Kozel, B. This phenomenon is supported by in vitro peptide studies, which note that increasing the space between PG motifs or removing prolines results in more ordered structures (Rauscher et al., 2006). Chem. Acad. Lysinonorleucine. doi: 10.7554/eLife.26526. Dermatol. Co-author Professor Anthony Weiss from the Charles Perkins Centre and Faculty of Science explained: "Tropoelastin can repair the heart because it is a precise replica of the body's natural elastic protein,". The isoform-function theory is further reinforced by the presence of two different ELN genes within teleosts that are differentially expressed both spatially and temporally during development (Miao et al., 2007). Elastin synthesis in arterial smooth muscle cell culture. Lyophilized Powder. By probing mutations in computational studies that resolve the atomistic structure of the molecule, the deduction of mechanisms associated with changes to functional roles of specific domains has become feasible, and a connection between local structures and biological performance can be established (Figure 2; Tarakanova et al., 2018). Tropoelastins domains each arise from single exons of the ELN gene. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. This suggests the ERCs primary signal pathways are involved in wound recognition through fragments of elastin, where EDPs are formed as a result of elastic tissue damage. J. Mol. Perturbation of either of these components greatly reduces tropoelastins ability to self-assemble in vitro and interact with the microfibril scaffold of elastic fibers (Nonaka et al., 2014), indicating that an intact domain 36 is required for correct assembly. into 200 nm then 12 m spherules, which eventually grow and stabilize into spherules 26 m in diameter (Clarke et al., 2006; Kozel et al., 2006; Tu and Weiss, 2010; Tu et al., 2010). Sci. 9:643110. doi: 10.3389/fbioe.2021.643110. J. Biochem. Four days after a heart attack, purified tropoelastin was injected into the heart. Bashir, M. M., Indik, Z., Yeh, H., Ornstein-Goldstein, N., Rosenbloom, J. C., Abrams, W., et al. Elastic fibers provide tissues with mechanical resilience, durability, and cell interactivity, which support a diverse range of specialized functionality. Biomacromolecules 20, 11781189. The elasticity of organs and tissues in vertebrates is due to the presence of elastin, and an insoluble protein whose soluble monomer, tropoelastin, is enzymatically cross-linked through -amino groups of lysine residues. doi: 10.1111/febs.14929, Hinderer, S., Shena, N., Ringuette, L. J., Hansmann, J., Reinhardt, D. P., Brucker, S. Y., et al. Biochim. Tropoelastin: a versatile, bioactive assembly module. (2008). 266, 308314. The Weiss Lab's research focuses on the use of human tropoelastin in tissue assembly and wound repair. Mater. Protein Eng. doi: 10.1016/j.jsb.2005.02.005, Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995). (2018). Pepe, A., Flamia, R., Guerra, D., Quaglino, D., Bochicchio, B., Pasquali Ronchetti, I., et al. doi: 10.1248/bpb.b13-00933, Ozsvar, J., Tarakanova, A., Wang, R., Buehler, M. J., and Weiss, A. S. (2019). 58, 270277. Biochemistry 8, 28372845. Chem. Provides infrastructure for further development and following approval to commercialize Elastagens products, SYDNEY February 7th: Elastagen Pty Limited, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced that it has entered into a definitive agreement under which Allergan, a leading global biopharmaceutical company, has agreed to acquire Elastagen for an upfront payment of US$95M plus contingent, commercial payments.. Structural changes and facilitated association of tropoelastin. Targeted modulation of tropoelastin structure and assembly. Communication: coacervation of tropoelastin results in fiber formation. Visconti, R. P., Barth, J. L., Keeley, F. W., and Little, C. D. (2003). 589(19 Pt A), 24772486. 281, 2375723765. 27, 441450. (2013). Positively charged lysine residues in domains 17 were identified to interact with negatively charged HS, most likely via ionic interactions (Lee et al., 2017). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The human ELN gene is located on the long arm of chromosome 7q11.2 and comprises of 34 exons nestled between lengthy introns (Indik et al., 1987, 1989; Bashir et al., 1989). doi: 10.1021/bi400760f, Miao, M., Reichheld, S. E., Muiznieks, L. D., Sitarz, E. E., Sharpe, S., and Keeley, F. W. (2017). Allergan announced that it would be accessing Elastagen's next generation Juvederm dermal filler injectable portfolio, which will now also boast its "key 'youth protein' tropoelastin". Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. Elastic fibers are eventually formed after extensive cross-linking through a process termed maturation (Yeo et al., 2016). Biomaterials 139, 163171. Allergan's Acquisition of Elastagen - Global Legal Chronicle 167, 94103. Allergan is an industry leader in Open Science,a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. Fibrillin-1 and -2 also interact with proteoglycans (Tiedemann et al., 2001), which coupled with tropoelastin/GAG interactions provide a pathway to the formation of elastic fibers. For this injection, the researchers used a new . 250, 9298. Direct observation of structure and dynamics during phase separation of an elastomeric protein. (2017). Med. A cell adhesive peptide from tropoelastin promotes sequential cell attachment and spreading via distinct receptors. Biopolymers 29, 16991706. doi: 10.1016/j.matbio.2006.08.258, Clarke, A. W., Arnspang, E. C., Mithieux, S. M., Korkmaz, E., Braet, F., and Weiss, A. S. (2006). J. Biol. Tropoelastin cannot readily be prepared in quantity from natural sources and this has limited research in several important areas including structure/function relationships and fiber assembly. doi: 10.1046/j.1432-1327.1999.00891.x, Yamauchi, Y., Tsuruga, E., Nakashima, K., Sawa, Y., and Ishikawa, H. (2010). Elastogenesis is the term that collectively describes the hierarchical process of elastic fiber formation, and is comprised of distinct phases: tropoelastin synthesis, coacervation, cross-linking, and deposition.
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