DOCSLIB.ORG

Biocompatibility of a Synthetic Biopolymer for the Treatment Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biocompatibility of a Synthetic Biopolymer for the Treatment Of perim Ex en l & ta a l ic O p in l h t C h f Journal of Clinical & Experimental a o Sarfare et al., J Clin Exp Ophthalmol 2015, 6:5 l m l a o n l r o DOI: 10.4172/2155-9570.1000475 g u y o J Ophthalmology ISSN: 2155-9570 ResearchResearch Article Article OpenOpen Access Access Biocompatibility of a Synthetic Biopolymer for the Treatment of Rhegmatogenous Retinal Detachment Shanta Sarfare1*, Yann Dacquay1, Syed Askari2, Steven Nusinowitz1 and Jean-Pierre Hubschman1 1Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA 2Medicus Biosciences, 2528 Qume Drive, Unit 1, San José, California 95131, USA Abstract Objective: The aim of this study is to evaluate the retinal safety and toxicity of a novel synthetic biopolymer to be used as a patch to treat rhegmatogenous retinal detachment. Methods: Thirty one adult wild type albino mice were divided in 2 groups. In Group A (n=9) 0.2 µl balanced salt solution (BSS) and in Group B (n=22), 0.2 µl biopolymer was injected in the subretinal space. Trans-scleral subretinal injection was performed in one eye and the fellow eye was used as control. In both groups, in vivo color fundus photography, electroretinogram (ERG), spectral domain optical coherence tomography (SD-OCT) were performed before injection and at days 7 and 14 post-intervention. Histological analysis was performed following euthanization at days 1, 7 and 21 post-injection. Results: The biopolymer was visualized in the subretinal space in vivo by SD-OCT and post-life by histology up to 1 week after the injection. There were no significant differences in ERG parameters between the two groups at 1 and 2 weeks post-injection. Minimal inflammatory response and loss of photoreceptor cells was only observed in the immediate proximity of the site of scleral perforation, which was similar in both groups. Overall integrity of the outer, inner retina and retinal pigment epithelial (RPE) layers was unaffected by the presence of the biopolymer in the subretinal space. Conclusions: Functional and histological evaluation suggests that the synthetic biopolymer is non-inflammatory and non-toxic to the eye. It may represent a safe therapeutic agent in the future, for the treatment of rhegmatogenous retinal detachment. Keywords: Retinal detachment; Retinal adhesive; Retinal tear which has the ability to effectively seal the retinal breaks in retinal detachment surgery. Introduction Polyethylene glycol (PEG) derivatives with molecular weights 10 Retinal detachment is the separation of the neurosensory retina from kilo Dalton (kDa) and higher are generally recognized as safe and non- the RPE, and is a potentially blinding ocular condition. Rhegmatogenous toxic [20] and therefore have been extensively used in medical devices retinal detachments are the most common type of retinal detachments and as drug carriers in pharmaceuticals applications [21-23]. Our and are secondary to retinal holes and/or breaks, which allow fluid study aims to evaluate the potential ocular and in particular the retinal from the vitreous cavity to enter the space between the RPE and the toxicity of a PEG-derived ophthalmic biopolymer through clinical, neurosensory retina. Individuals with myopia, as well as history of electrophysiological and histological evaluations. cataract surgery, trauma or ocular infections have a higher risk of developing rhegmatogenous retinal detachment [1-3]. Left untreated, a Methods chronic retinal detachment can lead to complications such as proliferative Animals vitreoretinopathy (PVR), vision loss and permanent blindness [4]. Albino Balb/c mice 6–8 weeks of age purchased from Jackson Standard treatment for rhegmatogenous retinal detachment Laboratories, ME maintained on 12/12 hours light/dark cycle were used involves scleral buckling and/or pars plana vitrectomy (PPV). in this study. All experiments were performed with IACUC-approved Endotamponade agents such as air, sulfur hexafluoride (SF6), protocols and following the ARVO Statement for the Use of Animals in octafluoropropane (C3F8) gas or silicone oil are used to maintain Ophthalmic and Vision Research. the retina in place and reduce fluid flow through the retinal opening until the retinopexy scar heals [5-8]. Although tamponade agents are successful in achieving reattachment, they have several disadvantages *Corresponding author: Shanta Sarfare, Ora, Inc., 300 Brickstone Square, such as head positioning, travel restrictions, limited vision for up to 2 Andover, Massachusetts, USA, Tel: 978-685-8900 extension 9532; Fax: 978-689- months, silicone oil adhesion to intraocular lenses, cataract, glaucoma, 0020; E-mail: [email protected] keratopathy and need for second surgery [9-13]. Received August 28, 2015; Accepted September 10, 2015; Published September 14, 2015 Some retinal adhesive products have been previously tested [14- Citation: Sarfare S, Dacquay Y, Askari S, Nusinowitz S, Hubschman JP (2015) 20]. The advantage of using retinal adhesives is that they can be used Biocompatibility of a Synthetic Biopolymer for the Treatment of Rhegmatogenous as a patch to cover and seal the retinal holes and/or retinal breaks and Retinal Detachment. J Clin Exp Ophthalmol 6: 475. doi: 10.4172/2155- eliminate the need for gas or silicone oil tamponade. However, these 9570.1000475 agents demonstrated severe retinotoxicity, inflammatory reaction, Copyright: © 2015 Sarfare S, et al. This is an open-access article distributed under difficulty of delivery or limited efficacy [14,15,17,19]. There is currently the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and no product available that is non-toxic to the ocular structures and source are credited. J Clin Exp Ophthalmol ISSN: 2155-9570 JCEO, an open access journal Volume 6 • Issue 5 • 1000475 Citation: Sarfare S, Dacquay Y, Askari S, Nusinowitz S, Hubschman JP (2015) Biocompatibility of a Synthetic Biopolymer for the Treatment of Rhegmatogenous Retinal Detachment. J Clin Exp Ophthalmol 6: 475. doi: 10.4172/2155-9570.1000475 Page 2 of 8 Generation of the ophthalmic biopolymer Functional evaluation The ophthalmic pre-formulation developed by Medicus Electroretinography (ERG): Dark adapted rod-mediated ERGs Biosciences (San José, California) comprises of three compounds: were recorded to blue flashes (Wratten 47A, maxλ =470 nm). Bilateral one containing 8 nucleophilic groups (8-arm-PEG 20K amine), the ERG recordings were performed on 16 mice, at baseline 1 week prior second also containing 8 nucleophilic groups and 8 degradable acetate and 1 and 2-weeks post injection, as previously described [29]. ERGs groups (8-arm-PEG 20K amine acetate) and the third containing 4 were recorded from the cornea using a gold loop electrode, referenced electrophilic groups (4-arm-PEG 20K amide ester) in a stoichiometric to a similar gold wire in the mouth. The mouse eye was positioned in ratio; an aqueous buffer and a viscosity enhancer [24-27]. The polymer front of an opening in a large integrating sphere in which brief flashes was designed to be degraded in 2-weeks by selecting degradable acetate of light at 1 Hz interval were presented. Responses were amplified groups, numbers of crosslinking sites and the polymer concentration in 10,000 × (Grass P511 High Performance AC Amplifier), band-pass the solution. Retinal adherence and the viscosity of the polymer were filtered (0.1-300 Hz), digitized using an I/O board (PCI-6221; National enhanced with the use of hydroxyl methyl propyl methyl cellulose. The Instruments, Austin, TX) and averaged. polymer demonstrated in previous study similar adhesive properties as Histological evaluation: Light, electron microscopy and the retina when tested in our laboratory [28]. All reactive PEG materials immunocytochemistry. were purchased from JenKem Corp, Plano, Texas. The firmness, adhesion, and elastic modulus of the polymer were characterized by Paraffin embedded tissue (FFPE): Eyes from mice (group A, n=3; a Texture Analyzer (TA.XT.plus) with Exponent software (v6.0) using group B, n=13) 3 weeks post-injection were fixed in 10% neutral buffered various probes. The components in the injection kit were mixed, formalin, paraffin embedded and sectioned. Consecutive 5-μm sections filtered and injected into the subretinal space as a liquid biopolymer were stained with hematoxylin and eosin (H&E) for light microscopy which solidifies at pH 7.4 at a pre-set time of 90–300 sec and adheres and processed for TUNEL labeling or immunohistochemistry. to the tissue. Plastic embedded tissue: Mouse eyes (group A, n=3; group B, Subretinal injections n=6) were oriented with respect to site of injection using cautery iron or tissue marker pen, fixed with a mixture of 2% paraformaldehyde: Eyes were dilated with 2.5% phenylephrine (HUB Pharmaceuticals, 2.5% glutaraldehyde in 0.1M sodium phosphate buffer (pH 7.4) and Rancho Cucamonga, CA) and 0.5% tropicamide (Akorn processed as previously described [30]. Sections of 1µm thickness Pharmaceuticals, Lake Forest, IL). Mice were anesthetized with stained with Toluidine blue were imaged with a Zeiss Axiophot ketamine (100 mg/kg; Phoenix Pharmaceuticals) and xylazine (8 mg/ microscope and ultra-thin sections stained with uranium and lead salts kg; Lloyd Laboratories). Goniovisc (2.5%) (HUB Pharmaceuticals, were imaged using Zeiss EM910 electron microscope. Rancho Cucamonga, CA) was applied to the eye to maintain corneal
Load more

Recommended publications
  • A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds
    polymers Review A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds M. Sai Bhargava Reddy 1 , Deepalekshmi Ponnamma 2 , Rajan Choudhary 3,4,5 and Kishor Kumar Sadasivuni 2,* 1 Center for Nanoscience and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad 500085, India; [email protected] 2 Center for Advanced Materials, Qatar University, Doha P.O. Box 2713, Qatar; [email protected] 3 Rudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Faculty of Materials Science and Applied Chemistry, Institute of General Chemical Engineering, Riga Technical University, Pulka St 3, LV-1007 Riga, Latvia; [email protected] 4 Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, LV-1007 Riga, Latvia 5 Center for Composite Materials, National University of Science and Technology “MISiS”, 119049 Moscow, Russia * Correspondence: [email protected] Abstract: Tissue engineering (TE) and regenerative medicine integrate information and technology from various fields to restore/replace tissues and damaged organs for medical treatments. To achieve this, scaffolds act as delivery vectors or as cellular systems for drugs and cells; thereby, cellular material is able to colonize host cells sufficiently to meet up the requirements of regeneration and repair. This process is multi-stage and requires the development of various components to create the desired neo-tissue or organ. In several current TE strategies, biomaterials are essential compo- nents. While several polymers are established for their use as biomaterials, careful consideration of the cellular environment and interactions needed is required in selecting a polymer for a given Citation: Reddy, M.S.B.; Ponnamma, application.
    [Show full text]
  • Bioplastics: Biobased Plastics As Renewable And/Or Biodegradable Alternatives to Petroplastics
    BIOPLASTICS: BIOBASED PLASTICS AS RENEWABLE AND/OR BIODEGRADABLE ALTERNATIVES TO PETROPLASTICS 1. Introduction ‘‘Plastics’’ were introduced approximately 100 years ago, and today are one of the most used and most versatile materials. Yet society is fundamentally ambivalent toward plastics, due to their environmental implications, so interest in bioplastics has sparked. According to the petrochemical market information provider ICIS, ‘‘The emergence of bio-feedstocks and bio-based commodity polymers production, in tandem with increasing oil prices, rising consumer consciousness and improving economics, has ushered in a new and exciting era of bioplastics commercialization. However, factors such as economic viability, product quality and scale of operation will still play important roles in determining a bioplastic’s place on the commer- cialization spectrum’’ (1). The annual production of synthetic polymers (‘‘plastics’’), most of which are derived from petrochemicals, exceeds 300 million tons (2), having replaced traditional materials such as wood, stone, horn, ceramics, glass, leather, steel, concrete, and others. They are multitalented, durable, cost effective, easy to process, impervious to water, and have enabled applications that were not possible before the materials’ availability. Plastics, which consist of polymers and additives, are defined by their set of properties such as hardness, density, thermal insulation, electrical isolation, and primarily their resistance to heat, organic solvents, oxidation, and microorgan- isms. There are hundreds of different plastics; even within one type, various grades exist (eg, low viscosity polypropylene (PP) for injection molding, high viscosity PP for extrusion, and mineral-filled grades). Applications for polymeric materials are virtually endless; they are used as construction and building material, for packaging, appliances, toys, and furniture, in cars, as colloids in paints, and in medical applications, to name but a few.
    [Show full text]
  • Cellulose Nanofibers and Other Biopolymers for Biomedical
    applied sciences Review Cellulose Nanofibers and Other Biopolymers for Biomedical Applications. A Review John Moohan 1, Sarah A. Stewart 1, Eduardo Espinosa 2 , Antonio Rosal 3, Alejandro Rodríguez 2 , Eneko Larrañeta 1 , Ryan F. Donnelly 1 and Juan Domínguez-Robles 1,* 1 School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; [email protected] (J.M.); [email protected] (S.A.S.); [email protected] (E.L.); [email protected] (R.F.D.) 2 Chemical Engineering Department, Faculty of Science, University of Córdoba, Building Marie-Curie, Campus of Rabanales, 14014 Córdoba, Spain; [email protected] (E.E.); [email protected] (A.R.) 3 Molecular Biology and Biochemical Engineering Department, University Pablo de Olavide, 41013 Sevilla, Spain; [email protected] * Correspondence: [email protected]; Tel.: +44-(0)28-9097-2360 Received: 30 October 2019; Accepted: 16 December 2019; Published: 20 December 2019 Abstract: Biopolymers are materials synthesised or derived from natural sources, such as plants, animals, microorganisms or any other living organism. The use of these polymers has grown significantly in recent years as industry shifts away from unsustainable fossil fuel resources and looks towards a softer and more sustainable environmental approach. This review article covers the main classes of biopolymers: Polysaccharides, proteins, microbial-derived and lignin. In addition, an overview of the leading biomedical applications of biopolymers is also provided, which includes tissue engineering, medical implants, wound dressings, and the delivery of bioactive molecules. The future clinical applications of biopolymers are vast, due to their inherent biocompatibility, biodegradability and low immunogenicity.
    [Show full text]
  • Review on Nanovaccination
    e-ISSN:2322-0139 Research and Reviews: Journal of Pharmacological and Toxicological Studies p-ISSN:2322-0120 Review on Nanovaccination Mamatha M* Prist University, Tanjore, Tamil Nadu, India Review Article Received: 15/11/2016 ABSTRACT Revised: 21/11/2016 Accepted: 28/11/2016 Nanotechnology, in spite of not a recent concept, has gained notable power in recent years. *Corresponding author: Because of the current approach in nano- engineering and material science in the previous Mamatha M, Prist University, Tanjore, Tamil Nadu, India, tenner, the nanoparticles have become Tel: +91 9133032626. astonishingly notable for their applications mainly in the fields of medicine and biology. Nanovaccine Email: [email protected] is a book approach to the vaccination methodology. Nanomaterials are transported in the form of Keywords: Nanovaccines, Encapsulation, Immunogenicity, nanobeads, microspheres, or micro- Nanoemulsion, Biocompatibility. nanoprojections. Trouble-free, successful and guarded needle-free routes such as patches of microprojections or intranasal or the oral route, or directly to the skin are few of the approaches which are mainly in the experimental phase at available but have a substantial destiny henceforth in nanovaccination. INTRODUCTION Nanovaccines Nanovaccines [1-10] are vaccines that mainly consist of nanoparticles and are ascend as an un used class of vaccines that straightly target the location in the body where the infection or disease emanate, as incompatible to conventional stimulants which may affect total parts of the body [11-20]. Number of advantages have been shown by different researchers explore and running the different features related to Nanovaccine [21-30]. NANOVACCINES ADVANTAGES Required dose on antigen is small, antigen presenting cells improved systematic processing and longtime stability during storage Extensive usage of antigen encapsulation [31-49] as it is fluent to discharge Because of slow release of the antigen single dose is sufficient for effective response.
    [Show full text]
  • Preliminary Fabrication of Biodegradable Polymer Membranes from Renewable Resources
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UTHM Institutional Repository i PRELIMINARY FABRICATION OF BIODEGRADABLE POLYMER MEMBRANES FROM RENEWABLE RESOURCES NUR SURAYA ANIS BT AHMAD BAKHTIAR A project report submitted in partial fulfillment of the requirements for the award of the Degree of Master of Mechanical Engineering Faculty of Mechanical and Manufacturing Engineering Universiti Tun Hussein Onn Malaysia DECEMBER 2011 iv ABSTRACT A membrane is an interphase between two adjacent phases acting as a selective barrier, regulating the transport substances between the two components. Microporous membranes with controlled pore size and structure were produce from biodegradable polymer based on vegetable oil monomer using phase inversion technique. The optimal conditions for the preparation of microporous polymer membranes was polymer concentrations in N,N-dimethylformamide (DMF) solution 12% (w/v), 15% (w/v), 18% (w/v) and 21% (w/v). The result, the membranes show two types of structure: pinhole- like structure and interconnected network structure. The structure of the membranes consisted of thick fibrillar elements. The membrane cross-section seemed to be composed of stacks of separate layers. Permeability of the polymer membranes obtained at lower concentrations, exhibit extremely higher water permeability with value 0.160952, 0.01482, 0.00098 and 0.00051 L/s.m3 for 12%, 15%, 18% and 21% (w/v) respectively. As the concentration increases, the surface layer of the membranes becomes thicker. Thus, the membranes are easily break compared to the membranes that have densely packed as shown by tear test of 12%, 15%, 18%, and 21% (w/v) with 21.8495 N/mm, 13.9566 N/mm, 10.5433 N/mm, and 12.1662 N/mm tear strength respectively.
    [Show full text]
  • Vesicular Stomatitis Virus Complexes for Therapy Of
    Institut für diagnostische und interventionelle Radiologie Klinikum rechts der Isar der Technischen Universität München Optimization and Characterization of Magnetic Nano Particle - Vesicular Stomatitis Virus complexes for Therapy of Hepatocellular Carcinoma Florian Wille Vollständiger Abdruck der von der Fakultät für Medizin der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Medizin (Dr. med.) genehmigten Dissertation. Vorsitzender: Prof. Dr. Ernst J. Rummeny Prüfer der Dissertation: 1. Priv.-Doz. Dr. Rickmer Braren 2. Prof. Dr. Roland M. Schmid Die Dissertation wurde am 23.12.2015 bei der Technischen Universität München eingereicht und durch die Fakultät für Medizin am 25.06.2017 angenommen. 1 Content 2 Abbreviations ....................................................................................................... 4 3 Introduction .......................................................................................................... 6 3.1 Hepatocellular Carcinoma: a “rising tide from east to west” (Monsour Jr, Asham et al. 2013) .... 6 3.2 Oncolytic Virotherapy with Vesicular Stomatitis Virus ................................................................. 9 3.3 Magnetic targeting with magnetic nanoparticles .......................................................................... 10 3.4 Aim of this study ........................................................................................................................... 11 3.5 Physical/biochemical background ................................................................................................
    [Show full text]
  • Study of Thermal and Mechanical Properties of a Biocomposite Based on Natural Rubber and 45S5 Bioglassò Particles
    J Therm Anal Calorim (2018) 131:735–742 https://doi.org/10.1007/s10973-016-5933-5 Study of thermal and mechanical properties of a biocomposite based on natural rubber and 45S5 BioglassÒ particles 1 2 2 1 3 M. J. Silva • V. O. Soares • G. C. Dias • R. J. Santos • A. E. Job • 4 4 A. O. Sanches • J. A. Malmonge Received: 18 June 2016 / Accepted: 26 October 2016 / Published online: 11 November 2016 Ó Akade´miai Kiado´, Budapest, Hungary 2016 Abstract Biocomposites based on natural rubber (NR) improved the mechanical properties of the samples. The reinforced with 45S5 BioglassÒ (BG) particles were samples became more rigid with the increasing quantity of obtained by casting/evaporation method in which NR was BG, as demonstrated by decreasing deformation and the dissolved in chloroform and mixed with BG particles. increasing elastic modulus (Y) and breaking strength of the Structural, mechanical, and thermal tests were performed samples. The BG particles positively affected the on the biocomposites to evaluate the influence of BG mechanical and thermal properties of the biocomposite, particles on the properties of the NR matrix. Thermo- allowing its use in biomedical applications. gravimetric tests (TG/DTG) of the biocomposites showed decomposition profiles similar to that of NR, and the main Keywords Biocomposite Á Natural rubber Á BioglassÒ Á peak of the DTG curve was well defined in the temperature Thermal analysis Á Mechanical analysis range 300–450 °C, characteristic of the structural degra- dation of NR. The TG analysis also revealed that the thermal stability of the samples increases with the Introduction increasing quantity of BG in the biocomposite.
    [Show full text]
  • Overcoming Contemporary Obstacles in Drug Delivery Via Acetalated Dextran Particle Formulations
    University of Rhode Island DigitalCommons@URI Open Access Dissertations 2019 OVERCOMING CONTEMPORARY OBSTACLES IN DRUG DELIVERY VIA ACETALATED DEXTRAN PARTICLE FORMULATIONS Nishan K. Shah University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/oa_diss Recommended Citation Shah, Nishan K., "OVERCOMING CONTEMPORARY OBSTACLES IN DRUG DELIVERY VIA ACETALATED DEXTRAN PARTICLE FORMULATIONS" (2019). Open Access Dissertations. Paper 834. https://digitalcommons.uri.edu/oa_diss/834 This Dissertation is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Dissertations by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. OVERCOMING CONTEMPORARY OBSTACLES IN DRUG DELIVERY VIA ACETALATED DEXTRAN PARTICLE FORMULATIONS BY NISHAN KALPESH SHAH A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN PHARMACEUTICAL SCIENCES UNIVERSITY OF RHODE ISLAND 2019 DOCTOR OF PHILOSOPHY DISSERTATION OF NISHAN KALPESH SHAH APPROVED: Dissertation Committee: Major Professor Samantha A. Meenach Jie Shen Michael Greenfield Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL UNIVERSITY OF RHODE ISLAND 2019 ABSTRACT Particle-based delivery systems have been investigated for their potential to increase the efficacy of patient diagnoses and treatments. In many cases, these systems increase the bioavailability and/or decrease the toxicity of clinically relevant drugs. These developments have led to improvements in patient compliance, morbidity, mortality, and quality of life. To date, particle-based delivery systems have been evaluated in hundreds of clinical trials around the world. Unlike conventional delivery systems, particle-based delivery systems offer increased surface area, colloidal stability, and system tunability, all of which can be tailored to target the disease state of interest and specific patient population.
    [Show full text]
  • (Plms): a Journey from Peptide Bond Isosteres to Gramicidin S Mimetics and Mitochondrial Targeting Agents
    764 CHIMIA 2009, 63, No. 11 SWISS CHEMISTS IN THE USA doi:10.2533/chimia.2009.764 Chimia 63 (2009) 764–775 © Schweizerische Chemische Gesellschaft Peptide-Like Molecules (PLMs): A Journey from Peptide Bond Isosteres to Gramicidin S Mimetics and Mitochondrial Targeting Agents Peter Wipf*, Jingbo Xiao, and Corey R. J. Stephenson Abstract: Peptides are natural ligands and substrates for receptors and enzymes and exhibit broad physiological effects. However, their use as therapeutic agents often suffers from poor bioavailability and insufficient membrane permeability. The success of peptide mimicry hinges on the ability of bioisosteres, in particular peptide bond replacements, to adopt suitable secondary structures relevant to peptide strands and position functional groups in equivalent space. This perspective highlights past and ongoing studies in our group that involve new methods development as well as specific synthetic library preparations and applications in chemical biology, with the goal to enhance the use of alkene and cyclopropane peptide bond isosteres. Keywords: Alkene peptide bond isosteres · Cyclopropanes · Gramicidin S · Mitochondrial targeting · Organic synthesis Peter Wipf was born 1. Introduction effective disruptors of protein–protein in Aarau, Switzer- interactions, and, in many instances, al- land. He received his Biopolymers represent a special class lowing for useful therapeutic activities. A Dipl. Chem. in 1984 of natural products, offering unique op- Sunesis-Merck collaboration discovered and his PhD in 1987 portunities for small molecule mimicry. aminoethylene isosteres 1 as potent in- from the University Biopolymer-derived compounds can ex- hibitors of the β-site amyloid precursor of Zurich under the ploit drug–target contacts that closely protein cleaving enzyme (Fig.
    [Show full text]
  • Development of Diverse Hydrogels from the Protean Polymer, Elastin-Like Polypeptide
    Development of Diverse Hydrogels from the Protean Polymer, Elastin-like Polypeptide By Malav S. Desai A dissertation submitted in partial satisfaction of the requirements for the degree of Joint Doctor of Philosophy with University of California, San Francisco in Bioengineering in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Seung-Wuk Lee, Chair Professor Tejal Desai Professor Ting Xu Fall 2017 Development of Diverse Hydrogels from the Protean Polymer, Elastin-like Polypeptide © Copyright 2017 by Malav S. Desai To Elaine & my parents 1 Abstract Development of Diverse Hydrogels from the Protean Polymer, Elastin-like Polypeptide by Malav S. Desai Joint Doctor of Philosophy in Bioengineering with University of California, San Francisco University of California, Berkeley Professor Seung-Wuk Lee, Chair Hydrogels have been used to develop scaffolds to address challenges in tissue engineering and drug delivery for several decades. The major advantage of using hydrogels is that their high water content and low stiffness enables them to mimic tissue- like environments. In my work, I develop four unique hydrogels using a single polymer, elastin-like polypeptide. The first challenge I address is that of hydrogel extensibility. Typical hydrogels cannot undergo large strains, which limits their durability and applicability to active tissues such as muscles. I use ELP to create a rubber-like elastic hydrogel that can stretch to 15 times its original length. Unlike most previous ELP hydrogels, our gels can reach such high strains due to the well-defined structure of our materials with minimal crosslinks. Next, I focus on developing an adhesive hydrogel using ELP.
    [Show full text]
  • Scientists Celebrate 50 Years Since Key RNA Discovery Rich Recalls Birth of a ‘Founding Technology’ for Biotech
    Volume 51 – Number 14 Wednesday – January 10, 2007 TechTalk S ERVING T HE M I T C OMMUNITY Scientists celebrate 50 years since key RNA discovery Rich recalls birth of a ‘founding technology’ for biotech Profound doubts were the frequent response when such a thing was possible and could work.” MIT biophysicist Alexander Rich announced that two sin- The seminal discovery of double-stranded RNA by Rich gle-strand ribonucleic acid (RNA) molecules could spon- and Davies came only three years after James Watson and taneously align themselves to form a double helix, just Francis Crick stunned the scientific world by describing like those of their famous cousin, DNA. Many biologists DNA’s structure as a double helix. Watson and Crick not thought it impossible; the rest considered it unlikely. only described a structure but also suggested how inher- Today, 50 years later, it is abundantly clear that Rich— ited information—genetic information—is safely stored who made the discovery with David R. Davies while both and can be passed from one generation to the next. It was were working at the National Institute of Mental Health— a major milestone in the biosciences. was onto something big. In fact, it generated a paradigm In 1953, Rich—working with famed chemist Linus Paul- shift in the science of biology. The discovery changed how ing at Caltech—was using X-ray crystallography to try research is done at the molecular level and helped spawn to discover the structure of RNA, hoping to learn more what has become the global biotechnology revolution. about its role in life.
    [Show full text]
  • Expanding Canonical Spider Silk Properties Through a DNA Combinatorial Approach
    Expanding canonical spider silk properties through a DNA combinatorial approach The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Jaleel, Zaroug et al. "Expanding canonical spider silk properties through a DNA combinatorial approach." Materials 13 (16): 3596 ©2020 Author(s) As Published 10.3390/ma13163596 Publisher Multidisciplinary Digital Publishing Institute Version Final published version Citable link https://hdl.handle.net/1721.1/127688 Terms of Use Creative Commons Attribution Detailed Terms https://creativecommons.org/licenses/by/4.0/ materials Article Expanding Canonical Spider Silk Properties through a DNA Combinatorial Approach 1,2, 1,3, 1 1,4 Zaroug Jaleel y, Shun Zhou y, Zaira Martín-Moldes , Lauren M. Baugh , Jonathan Yeh 1,5 , Nina Dinjaski 1,6, Laura T. Brown 1,7, Jessica E. Garb 8 and David L. Kaplan 1,* 1 Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA; [email protected] (Z.J.); [email protected] (S.Z.); [email protected] (Z.M.-M.); [email protected] (L.M.B.); [email protected] (J.Y.); [email protected] (N.D.); [email protected] (L.T.B.) 2 School of Medicine, Boston University, Boston, MA 02118, USA 3 National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China 4 Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames St #56-651, Cambridge, MA 02142, USA 5 Department of Process Development, Akouos Inc., 645 Summer St. Boston, MA 02210, USA 6 Division of Innovation, Partners HealthCare Innovation, 215 First Street, Cambridge, MA 02142, USA 7 Department of Research Solutions North America, MilliporeSigma, 400 Summit Dr, Burlington, MA 01803, USA 8 Department of Biological Science, University of Massachusetts Lowell, 198 Riverside Street, Olsen Hall 234, Lowell, MA 01854, USA; [email protected] * Correspondence: [email protected] These authors contributed equally to this work.
    [Show full text]