DOCSLIB.ORG

Silk Fibroin: Structural Implications of a Remarkable Amino Acid Sequence

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Silk Fibroin: Structural Implications of a Remarkable Amino Acid Sequence http://www.paper.edu.cn PROTEINS:Structure,Function,andGenetics44:119–122(2001) SilkFibroin:StructuralImplicationsofaRemarkable AminoAcidSequence Cong-ZhaoZhou,1,2,3 FabriceConfalonieri,1 MichelJacquet,1 RolandPerasso,2 Zhen-GangLi,3 andJoelJanin4* 1InstitutdeGe´ne´tiqueetMicrobiologie,Universite´Paris-SudetCNRS,OrsayCedex,France 2LaboratoiredeBiologieCellulaire4,Universite´Paris-SudetCNRS,OrsayCedex,France 3DepartmentofBiology,UniversityofScienceandTechnologyofChina,Hefei,Anhui,People’sRepublicofChina 4Laboratoired’EnzymologieetBiochimieStructurales,CNRS,Gif-sur-Yvette,France ABSTRACT Theaminoacidsequenceofthe minedproteinsequenceofthefibroinheavychaindeduced heavychainofBombyxmorisilkfibroinwasderived fromthatofthegenomicDNA.4 fromthegenesequence.The5,263-residue(391-kDa) polypeptidechaincomprises12low-complexity SEQUENCEANDCOMPOSITIONOFTHE “crystalline”domainsmadeupofGly–Xrepeatsand FIBROINHEAVYCHAIN covering94%ofthesequence;XisAlain65%,Serin Aftertheearlystudiesmentionedaboveandreviewedby 23%,andTyrin9%oftherepeats.Theremainder Lucasetal.,1 Bombyxsilkfibroinreceivedlittleattention includesanonrepetitive151-residueheaderse- frombiochemists.Thesequenceofthe26-kDalightchain, quence,11nearlyidenticalcopiesofa43-residue ofashortinternalfragmentandofa85-residueC-terminal spacersequence,anda58-residueC-terminalse- sequenceoftheheavychainweredetermined.5–7 Thelight quence.Theheadersequenceishomologoustothe chain,whichislinkedtotheheavychainbyasingle N-terminalsequenceofotherfibroinswithacom- disulfidebridge,hasastandardaminoacidcomposition pletelydifferentcrystallineregion.InBombyxmori, andanonrepetitivesequence.Itplaysonlyamarginalrole eachcrystallinedomainismadeupofsubdomains inthefiber. ofϳ70residues,whichinmostcasesbeginwith Thecompleteaminoacidsequenceoftheheavychain repeatsoftheGAGAGShexapeptideandterminate hasnowbeendeducedfromthatofa80-kbpfragmentof withtheGAAStetrapeptide.Withinthesubdo- BombyxmorigenomicDNAcomprisingthe17-kpbfibroin mains,theGly–Xalternanceisstrict,whichstrongly gene(accesscodeGenBankAF226688–EMBLP05790).4 supportstheclassicPauling–Coreymodel,inwhich Thegenecodesforapolypeptidechainof5,263residues ␤-sheetspackoneachotherinalternatinglayersof withamolecularweightof391kDa,composedof45.9% Gly/GlyandX/Xcontacts.Whenfittingtheactual glycine,30.3%alanine,12.1%serine,5.3%tyrosine,1.8% sequencetothatmodel,weproposethateachsubdo- valine,andonly4.7%oftheother15aminoacidtypes. mainformsa␤-strandandeachcrystallinedomain Mostofthesequenceislow-complexityandforms2,377 atwo-layered␤-sandwich,andwesuggestthatthe repeatsofaGly–X(GX)dipeptidemotif.TheGXrepeatis ␤-sheetsmaybeparallel,ratherthanantiparallel,as thebuildingblockofthe␤-sheetsinthePauling–Corey hasbeenassumeduptonow.Proteins2001;44:119–122. modelandofthewholefiber.Thesequencecontainsvery ©2001Wiley-Liss,Inc. longstretchesofGXrepeatsthatmustconstitutethex-ray Keywords:Bombyxmori;low-complexitysequences; diffractingstructure,oftencalledthe“crystalline”compo- ␤-sheetpacking;fiberstructure nentofsilkfibroin.ResidueXisAlain64%oftherepeats, Serin22%,Tyrin10%,Valin3%,andThrin1.3%ofthe INTRODUCTION repeats.Essentiallynoneoftheother14aminoacidtypes Thelongandrobustproteinfiberthatmakesupthe ispresentintherepeats.In2%ofthedipeptides,thefirst cocoonoftheBombyxmoricaterpillarhasbeenusedby positionisanalanineinsteadofglycine.Thisoccurs manformorethan3,000yearstoproducehigh-quality almostexclusivelyintheGAAStetrapeptide,whichis ϭ threadandcloth.Theirremarkablepropertiesoriginatein repeated41times.Moreover,twohexapeptidess ϭ thephysicalchemistryofsilkfibroin,theproteinthat GAGAGS,in433copies,andy GAGAGY,in120copies, constitutesalmostallthefiber.Fibroinissynthesizedin accountfor70%ofthelow-complexityregion.Theirabun- largequantitybythesilkglandofthecaterpillarastwo dancewasknownfrompartialsequencesanditwas polypeptidechainslinkedbyadisulfidebridge.Thelarger suggestedthatfibroinmightbemadeupentirelyofthese heavychainisglycinerich,andmostofitssequenceisa repeatofGly–Ala/Serdipeptides.Thesilkfiberhasbeen 1 Grantsponsor:ProgrammedesRecherchesAvance´esFranco- knownasearlyas1913todiffractx-rays. Itsdiffraction Chinois;Grantnumber:BT97-05. patternischaracteristicofapleated␤-sheet,andithelped *Correspondenceto:Joe`lJanin,LEBS-CNRS,91198Gif-sur-Yvette, PaulingandCoreyindefiningthistypeofsecondary [email protected] structure.2 ThePauling–Coreymodelofsilkfibroin3 is Received3November2000;Accepted5March2001 revisitedherewithinthecontextoftherecentlydeter- Publishedonline00Month2001 ©2001WILEY-LISS,INC. 中国科技论文在线 http://www.paper.edu.cn 120 C.-Z. ZHOU ET AL. Fig. 1. The silk fibroin heavy chain. The 5,263-residue polypeptide chain (EMBL P05790) is broken in domains and subdomains. The sequence number of the first residue number and the length l of each domain are given in parentheses. The 25-residue motif in boldface characters is repeated between the header and the linkers. A one-residue (or three-residue) insertion in subdomain GX9.4 is also in boldface characters. Lowercase letters s, y, a, and u represent frequently observed hexapeptides. Hexapeptide code and number of copies: s GAGAGS 433 y GAGAGY 120 a GAGAGA 27 ␮ GAGYGA 39 hexapeptides.6,8 Figure 1 shows that this is incorrect in fibroin is otherwise completely different from Bombyx.It spite of the hexapeptide abundance, and that fibroin has a yields a different type of fiber, and the bulk of its 2,639- more elaborate primary structure as discussed below. residue sequence (EMBL O76786), although low-complex- ity, is more alanine than glycine-rich.9 A BLAST search THE NONREPETITIVE OR “AMORPHOUS” against the Drosophila genome also suggests the presence SEGMENTS of a segment related to these N-terminal sequences in the The GX repeats that form the bulk of the polypeptide CG18026 gene product, but the score is much lower (27% chain are distributed among 12 domains separated by identity over 136 residues), and the protein function is short linkers (Fig. 1). In contrast to the domains, the unknown. N-terminal 151 residues, C-terminal 50 residues, and the The 58-residue C-terminal segment of the Bombyx heavy 42–43 residue linkers between domains are nonrepetitive chain is arginine/lysine-rich and depleted in hydrophobic and “amorphous,” as opposed to the “crystalline” domains. residues, which does not suggest a globular fold. It con- The N-terminal segment or header has a standard amino tains three cysteine residues involved in two disulfide acid composition and may constitute an independent globu- bonds,7 one with the light chain, the other internal. The 11 lar unit, possibly with some ␣-helix as well as a ␤-sheet. linker segments connecting the crystalline domains have Related sequences (33–38% identity) are found at the nearly identical sequences, including a 25-residue nonre- N-terminus of the fibroins of the moths Galleria mal- petitive peptide (boldface characters in Fig. 1), also present lonella and Antheraea pernyi (Fig. 2). The cocoon of the in the header sequence in a truncated version. The peptide latter is used in Asia to produce tussah silk. Antheraea breaks the GX alternance and terminates the crystalline 中国科技论文在线 http://www.paper.edu.cn SEQUENCE AND STRUCTURE OF SILK FIBROIN 121 collaborators proposed that the fiber is made of antiparal- lel ␤-sheets packing on top of each other.3 The ␤-strands extend along the fiber axis, yielding a 7.0-Å axial repeat containing two peptide units. There is also a Ϸ9.5-Å repeat across the fiber in the diffraction pattern. It is interpreted as representing in one direction, twice the spacing between ␤-strands in an antiparallel ␤-sheet, and in the orthogonal direction, twice the spacing between packed ␤-sheets. The Pauling–Corey model, elaborated upon by Crick and Ken- drew,10 takes note of the fact that, in a ␤-strand made of Gly–Ala/Ser repeats, all the nonglycine residues have their side-chains on the same face of the ␤-sheet. The ␤-sheets may then pack on each other alternatively by their glycine face and by their Ala/Ser face. The first Fig. 2. The header sequence. Secondary structure prediction by PHD and an alignment of the N-terminal sequences of silk fibroins from packing yields a short 3.5–3.9 Å spacing, the second longer Bombyx mori (EMBL P05790), Galleria mellonella (EMBL AF095239), one of 5.3–5.7 Å. This type of packing was later observed in and Antherea pernyi (EMBL O76786). E, extended; H, helical. crystalline poly-(Ala–Gly).11 The Pauling–Corey model was challenged in a recent study of the Bombyx silk fiber pattern. In an attempt to domains. It has a proline, charged residues and the only interpret the diffracted intensities quantitatively, Taka- tryptophan residue found in fibroin. Charged residues are hashi et al.12 test four ways of assembling ␤-strands and entirely absent from the crystalline domains. packing ␤-sheets. Adjacent strands within a ␤-sheet may either be parallel or antiparallel, and their side-chains PUNCTUATIONS IN THE CRYSTALLINE REGION may either all point in the same direction (polar mode) or The 12 crystalline domains are labeled GX1–GX12 in alternatively up and down (antipolar mode). With this Figure 1. Their average length is 413 residues, omitting convention, the Pauling–Corey model is polar–antiparal- GX12, which is much shorter (37 residues). Within a lel. It yields the best fit to a set of 26 diffracted intensities domain, the GX alternance is perturbed only by the assuming the fibroin sequence to be just poly-(Ala–Gly). occasional presence of a GAAS tetrapeptide, and, in do- Nevertheless, the authors go on to consider effects of main GX9, by a single residue
Load more

Recommended publications
  • Effect of Starch on Property of Silk Fibroin/Keratin Blend Films
    International Journal of GEOMATE, Dec., 2016, Vol. 11, Issue 28, pp.2870-2873 Special Issue on Science, Engineering and Environment, ISSN: 2186-2990, Japan EFFECT OF STARCH ON PROPERTY OF SILK FIBROIN/KERATIN BLEND FILMS Yaowalak Srisuwan, Ansaya Thonpho and Prasong Srihanam Faculty of Science, Mahasarakham University, Maha Sarakham 44150, Thailand ABSTRACT: This work was aimed to study the effect of starch on silk fibroin (SF)/keratin (K) blend films properties. The SF and K solutions were mixed with starch, homogeneously stirred and poured into polystyrene culture plates. The mixture solution was then dried in an oven at 40 °C for 3 days. The films were then investigated for their morphology, secondary structure and thermal properties by using scanning electron microscope (SEM), Fourier transform-infrared (FT-IR) spectrophotometer, Thermogravimetric analysis (TGA). The results found that each film had different patterns of surfaces depending on ratio used. The structure of almost films co-existed with random coil and α-helix structures which resulted to increase the flexibility and of film. The structure of the films changed to β-sheet after blending between SF and K according to H-bond formation and increased thermal stability of the films. This result indicated that starch helped to decrease the crystalline structure of the film which increased their flexibility. Keywords: Biopolymer, Morphology, Secondary structure, Thermal property 1. INTRODUCTION Silk fibroin (SF) solution was prepared by firstly boiling twice of B. mori cocoons in 0.5% (w/v) Silk is a natural fibrous protein produced from Na2CO3 solution at 90 °C for 30 min in each times, silkworm which had a unique characteristic.
    [Show full text]
  • Programming Function Into Mechanical Forms by Directed Assembly of Silk
    Programming function into mechanical forms by SEE COMMENTARY directed assembly of silk bulk materials Benedetto Marellia,1, Nereus Patela, Thomas Duggana, Giovanni Perottoa, Elijah Shirmana, Chunmei Lia, David L. Kaplana,b, and Fiorenzo G. Omenettoa,c,d,2 aSilklab, Department of Biomedical Engineering, Tufts University, Medford, MA 02155; bDepartment of Chemical Engineering, Tufts University, Medford, MA 02155; cDepartment of Electrical Engineering, Tufts University, Medford, MA 02155; and dDepartment of Physics, Tufts University, Medford, MA 02155 Edited by David A. Weitz, Harvard University, Cambridge, MA, and approved November 21, 2016 (received for review July 23, 2016) We report simple, water-based fabrication methods based on particular, three different models have been proposed for silk protein self-assembly to generate 3D silk fibroin bulk materials assembly, which have been supported by diverse experimental that can be easily hybridized with water-soluble molecules to evidences obtained from Bombyx mori silk, spider silk proteins, obtain multiple solid formats with predesigned functions. Con- regenerated silk fibroin, and recombinantly produced spider trolling self-assembly leads to robust, machinable formats that silk proteins at different concentrations (9–18). A recent review exhibit thermoplastic behavior consenting material reshaping at covers in detail these models (19). (i) The first mechanism the nanoscale, microscale, and macroscale. We illustrate the involves the formation of micellar nanostructures that fuse versatility of the approach by realizing demonstrator devices together via coalescence, forming microscopic globular struc- where large silk monoliths can be generated, polished, and tures that, in the presence of shear stress, elongate and fuse reshaped into functional mechanical components that can be together (9).
    [Show full text]
  • Silk-Based Biomaterials for Tissue Engineering
    C H A P T E R 1 Silk-based Biomaterials for Tissue Engineering V. Kearns, A.C. MacIntosh, A. Crawford and P.V. Hatton* Summary ilks are fibrous proteins, which are spun by a variety of species including silkworms and spiders. Silks have common structural components and have a hierarchical structure. Silkworm silk must be S degummed for biomedical applications in order to remove the immunogenic sericin coating. It may subsequently be processed into a variety of forms, often via the formation of a fibroin solution, including films, fibres and sponges, and used in combination with other materials such as gelatine and hydroxyapatite. Spider silks do not have a sericin coating and may be used in natural fibre form or processed via formation of a spidroin solution. Both silkworm and spider silks have been reported to support attachment and proliferation of a variety of cell types. Silks have subsequently been investigated for use in tissue engineering. This chapter provides a general overview of silk biomaterials, discussing their processing, biocompatibility and degradation behaviour and paying particular attention to their applications in tissue engineering. KEYWORDS: Silk; Fibroin; Spidroin; Tissue engineering. *Correspondence to: Professor Paul V Hatton, Centre for Biomaterials & Tissue Engineering, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA, UK. Email: [email protected] Tel: +44 (114) 271 7938 Fax: +44 (114) 279 7050. Topics in Tissue Engineering, Vol. 4. Eds. N Ashammakhi, R Reis, & F Chiellini © 2008. Kearns et al. Silk Biomaterials 1. INTRODUCTION Silks are fibrous proteins, which are spun into fibres by a variety of insects and spiders [1].
    [Show full text]
  • The Physiological Accumulation of Mutant Fibroin Light Chains Induces
    Journal of Insect Biotechnology and Sericology 86, 105-112 (2017) The physiological accumulation of mutant fibroin light chains induces an unfolded protein response in the posterior silk gland of the Sericin cocoon Nd-sD strain of silkworm Bombyx mori Tadashi Takahashi1, Masao Miyazaki1, Shin-ichiro Kidou2, Yoshiki Matsui1, Ying An1, Taku Ozaki3, Koichi Suzuki1＊＊ and Tetsuro Yamashita1＊ 1 Faculty of Agriculture, Iwate University, Ueda, Morioka, Iwate 020-8550, Japan 2 Graduate School of Natural Sciences, Nagoya City University, Mizuho-cho, Mizuho-ku, Nagoya 467-8501, Japan 3 Faculty of Science and Engineering, Iwate University, Ueda, Morioka, Iwate 020-8550, Japan (Received May 15, 2017; Accepted July 4, 2017) Fibroin, a major component of silk fiber, is composed of light (L) chains, heavy chains, and fhx/P25 in the silk- worm Bombyx mori. Sericin cocoon (Nd-sD) is a silkworm strain expressing a mutant fibroin L chain that is accu- mulated in the endoplasmic reticulum (ER) of posterior silk glands (PSGs). However, little is known about the effects of accumulation in PSGs in Nd-sD strain. We compared the PSG gene expression profiles of 5th-instar larvae of Nd-sD strain and the fibroin-producing normal strain. cDNA representational difference analysis identi- fied candidate genes whose expression levels were higher in Nd-sD strain than in normal strain. We focused on heat shock proteins and cathepsin B, a major lysosomal protease. We confirmed upregulation of BiP(GRP78), Hsp20.8, and cathepsin B at the transcriptional and/or translational levels. These results suggest that the accu- mulation of mutant L chain induces the unfolded protein response in PSGs of Nd-sD strain, which will be a valu- able tool for protein quality-control studies of silk grand.
    [Show full text]
  • A Review of Structure Construction of Silk Fibroin Biomaterials from Single Structures to Multi-Level Structures
    International Journal of Molecular Sciences Review A Review of Structure Construction of Silk Fibroin Biomaterials from Single Structures to Multi-Level Structures Yu Qi 1, Hui Wang 1,*, Kai Wei 1, Ya Yang 1, Ru-Yue Zheng 1, Ick Soo Kim 2 and Ke-Qin Zhang 1,* 1 National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China; [email protected] (Y.Q.); [email protected] (K.W.); [email protected] (Y.Y.); [email protected] (R.-Y.Z.) 2 Nano Fusion Technology Research Lab, Interdisciplinary Cluster for Cutting Edge Research (ICCER), Division of Frontier Fibers, Institute for Fiber Engineering (IFES), Shinshu University, Ueda, Nagano 386 8567, Japan; [email protected] * Correspondence: [email protected] (H.W.); [email protected] (K.-Q.Z.) Academic Editors: John G. Hardy and Chris Holland Received: 24 November 2016; Accepted: 11 January 2017; Published: 3 March 2017 Abstract: The biological performance of artificial biomaterials is closely related to their structure characteristics. Cell adhesion, migration, proliferation, and differentiation are all strongly affected by the different scale structures of biomaterials. Silk fibroin (SF), extracted mainly from silkworms, has become a popular biomaterial due to its excellent biocompatibility, exceptional mechanical properties, tunable degradation, ease of processing, and sufficient supply. As a material with excellent processability, SF can be processed into various forms with different structures, including particulate, fiber, film, and three-dimensional (3D) porous scaffolds. This review discusses and summarizes the various constructions of SF-based materials, from single structures to multi-level structures, and their applications.
    [Show full text]
  • Materials Fabrication from Bombyx Mori Silk Fibroin
    PROTOCOL Materials fabrication from Bombyx mori silk fibroin Danielle N Rockwood, Rucsanda C Preda, Tuna Yücel, Xiaoqin Wang, Michael L Lovett & David L Kaplan Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA. Correspondence should be addressed to D.L.K. ([email protected]). Published online 22 September 2011; doi:10.1038/nprot.2011.379 Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied protein polymer for biomaterial applications. Silk fibroin has remarkable mechanical properties when formed into different materials, demonstrates biocompatibility, has controllable degradation rates from hours to years and can be chemically modified to alter surface properties or to immobilize growth factors. A variety of aqueous or organic solvent-processing methods can be used to generate silk biomaterials for a range of applications. In this protocol, we include methods to extract silk from B. mori cocoons to fabricate hydrogels, tubes, sponges, composites, fibers, microspheres and thin films. These materials can be used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery. INTRODUCTION Bombyx mori (silkworm) silk is a unique material, which has his- blocks linked by small hydrophilic linker segments or spacers. torically been highly regarded for its strength and luster. Physicians The crystalline regions are primarily composed of glycine-X have used silk as a suture material for centuries, and it has recently repeats, where X is alanine, serine, threonine or valine. Within gained attention as a biomaterial because of several desirable prop- these domains lie subdomains that are rich in glycine, alanine, erties.
    [Show full text]
  • Thermal Conductivity of Protein-Based Materials: a Review
    polymers Review Thermal Conductivity of Protein-Based Materials: A Review Ye Xue 1,2, Samuel Lofland 1 and Xiao Hu 1,2,3,* 1 Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA; [email protected] (Y.X.); lofl[email protected] (S.L.) 2 Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA 3 Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ 08028, USA * Correspondence: [email protected]; Tel.: +1-856-256-4860; Fax: +1-856-256-4478 Received: 19 February 2019; Accepted: 7 March 2019; Published: 11 March 2019 Abstract: Fibrous proteins such as silks have been used as textile and biomedical materials for decades due to their natural abundance, high flexibility, biocompatibility, and excellent mechanical properties. In addition, they also can avoid many problems related to traditional materials such as toxic chemical residues or brittleness. With the fast development of cutting-edge flexible materials and bioelectronics processing technologies, the market for biocompatible materials with extremely high or low thermal conductivity is growing rapidly. The thermal conductivity of protein films, which is usually on the order of 0.1 W/m·K, can be rather tunable as the value for stretched protein fibers can be substantially larger, outperforming that of many synthetic polymer materials. These findings indicate that the thermal conductivity and the heat transfer direction of protein-based materials can be finely controlled by manipulating their nano-scale structures. This review will focus on the structure of different fibrous proteins, such as silks, collagen and keratin, summarizing factors that can influence the thermal conductivity of protein-based materials and the different experimental methods used to measure their heat transfer properties.
    [Show full text]
  • New Insights Into the Proteins Interacting with the Promoters Of
    www.nature.com/scientificreports OPEN New insights into the proteins interacting with the promoters of silkworm fbroin genes Yan Ma1,2, Qin Luo1,2, Yao Ou1, Yiyun Tang1, Wenhui Zeng1, Haomiao Wang1, Jie Hu1 & Hanfu Xu1* The silkworm, Bombyx mori, is a silk-producing insect that has contributed greatly to human society. The silk gland of B. mori is a specialized organ responsible for synthesizing silk fbroin and sericin proteins under control of numerous factors. However, which factors are involved in direct silk protein synthesis regulation remains largely unknown. We report the identifcation of promoter-interacting proteins (PIPs) necessary for the regulation of genes encoding fbroin proteins, including the fbroin heavy chain (fbH), fbroin light chain (fbL), and a 25-kD polypeptide protein (P25). In the fourth larval molting stage (M4) or day 5 ffth-instar larvae (L5D5), a total of 198, 292, and 247 or 330, 305, and 460 proteins interacting with the promoter region of fbH, fbL and P25, respectively, were identifed from the posterior silk gland by DNA pull-down combined with mass spectrometry. Many PIPs were particularly involved in ribosome- and metabolism-related pathways. Additionally, 135 and 212 proteins were identifed as common PIPs of fbH, fbL and P25 in M4 and L5D5, respectively. Among all PIPs, we identifed 31 potential transcription factors, such as Y-box and poly A-binding proteins, which play roles in nucleotide binding, ATP binding, or protein folding. This study provides the frst in-depth profle of proteins interacting with fbroin gene promoters and contributes to a better understanding of silk protein synthesis regulation.
    [Show full text]
  • Silk Fibroin: a Smart Biomaterial for Long Term and Targeted Nanotherapeutics
    SILK FIBROIN: A SMART BIOMATERIAL FOR LONG TERM AND TARGETED NANOTHERAPEUTICS Tapash Chakraborty, Anupam Sarma* & Malay K. Das Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam, India Abstract: With the advancement of chemical and polymer sciences, the various strategies have been grown up for the development of novel Nanotherapeutics. Controlled Release Drug Delivery strategy has also been utilized by the novel Nanoformulations to alter the pharmacokinetic and pharmacodynamic property of drugs as well as to target the drug at different sites inside the body. Drug carrier materials play a significant role in the delivery of drugs. These carriers are processed into different drug controlled release systems. As the time passed the preference for biodegradable biomaterials have been increasing day by day. The biomaterial is those substances that have been engineered to interact with biological systems for therapeutic or diagnostic purposes. Biomaterials are mainly derived from natural materials but are can also be synthesized in the laboratory. Silk fibroin (SF) is a natural protein polymer that has been approved as a biomaterial by the US Food and Drug Administration (FDA). Silk fibroin based materials have a great biocompatibility profile due to their cytocompatibility and relatively lower or similar immunogenic potential compared to other common degradable polymers. SF has many unique characteristics, including appropriate mechanical properties, versatile process ability in an aqueous environment, biocompatibility, and a controlled degradation rate that make it an excellent candidate for drug delivery applications. So far silk-based nanoparticles have been developed to target lung, tumor and ocular disease for the delivery of proteins, small molecules, and anticancer drugs.
    [Show full text]
  • N-Terminal Domain of Bombyx Mori Fibroin Mediates the Assembly of Silk in Response to Ph Decrease
    doi:10.1016/j.jmb.2012.02.040 J. Mol. Biol. (2012) 418, 197–207 Contents lists available at www.sciencedirect.com Journal of Molecular Biology journal homepage: http://ees.elsevier.com.jmb N-Terminal Domain of Bombyx mori Fibroin Mediates the Assembly of Silk in Response to pH Decrease Yong-Xing He†, Nan-Nan Zhang†, Wei-Fang Li, Ning Jia, Bao-Yu Chen, Kang Zhou, Jiahai Zhang, Yuxing Chen and Cong-Zhao Zhou⁎ Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China Received 20 October 2011; Fibroins serve as the major building blocks of silk fiber. As the major received in revised form component of fibroin, the fibroin heavy chain is a considerably large protein 18 February 2012; comprising N-terminal and C-terminal hydrophilic domains and 12 highly accepted 23 February 2012 repetitive Gly-Ala-rich regions flanked by internal hydrophilic blocks. Here, Available online we show the crystal structure of the fibroin N-terminal domain (FibNT) at 1 March 2012 pH 4.7, revealing a remarkable double-layered anti-parallel β-sheet with each layer comprising two FibNT molecules entangled together. We also Edited by M. Moody show that FibNT undergoes a pH-responsive conformational transition from random coil to β-sheets at around pH 6.0. Dynamic light scattering Keywords: demonstrates that FibNT tends to oligomerize as pH decreases to 6.0, and fibroin; electron microscopy reveals micelle-like oligomers. Our results are X-ray crystallography; consistent with the micelle assembly model of silk fibroin and, more N-terminal domain; importantly, show that the N-terminal domain in itself has the capacity to structural transition; form micelle-like structures in response to pH decrease.
    [Show full text]
  • Silk Fibroin Safety in the Eye: a Review That Highlights a Concern
    BMJ Open Ophth: first published as 10.1136/bmjophth-2020-000510 on 23 September 2020. Downloaded from Review Silk fibroin safety in the eye: a review that highlights a concern Peter W Madden ,1,2 Igor Klyubin,3,4 Mark J Ahearne1,2 To cite: Madden PW, Klyubin I, ABSTRACT a review on silk in ophthalmology to consider Ahearne MJ. Silk fibroin The biomedical use of silk as a suture dates back to its safety in the eye. safety in the eye: a review antiquity. Fibroin is the structural element that determines that highlights a concern. the strength of silk and here we consider the safety of BMJ Open Ophthalmology fibroin in its role in ophthalmology. The high mechanical 2020;5:e000510. doi:10.1136/ THE ORIGIN AND APPLICATION OF SILK FIBROIN bmjophth-2020-000510 strength of silk meant sufficiently thin threads could IN THE EYE be made for eye microsurgery, but such usage was all Silks are produced primarily by species of but superseded by synthetic polymer sutures, primarily Euarthropoda, such as moths, spiders and Received 8 May 2020 because silk in its entirety was more inflammatory. centipedes. In general, the silk components Revised 15 July 2020 Significant immunological response can normally be Accepted 7 August 2020 avoided by careful manufacturing to provide high purity are stored in the organism as liquids, which fibroin, and it has been utilised in this form for tissue are then configured into fibres on extrusion. engineering an array of fibre and film substrata deployed The number of natural silks is very large, as in research with cells of the eye.
    [Show full text]
  • Booklet-The-Structures-Of-Life.Pdf
    The Structures of Life U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NIH Publication No. 07-2778 National Institutes of Health Reprinted July 2007 National Institute of General Medical Sciences http://www.nigms.nih.gov Contents PREFACE: WHY STRUCTURE? iv CHAPTER 1: PROTEINS ARE THE BODY’S WORKER MOLECULES 2 Proteins Are Made From Small Building Blocks 3 Proteins in All Shapes and Sizes 4 Computer Graphics Advance Research 4 Small Errors in Proteins Can Cause Disease 6 Parts of Some Proteins Fold Into Corkscrews 7 Mountain Climbing and Computational Modeling 8 The Problem of Protein Folding 8 Provocative Proteins 9 Structural Genomics: From Gene to Structure, and Perhaps Function 10 The Genetic Code 12 CHAPTER 2: X-RAY CRYSTALLOGRAPHY: ART MARRIES SCIENCE 14 Viral Voyages 15 Crystal Cookery 16 Calling All Crystals 17 Student Snapshot: Science Brought One Student From the Coast of Venezuela to the Heart of Texas 18 Why X-Rays? 20 Synchrotron Radiation—One of the Brightest Lights on Earth 21 Peering Into Protein Factories 23 Scientists Get MAD at the Synchrotron 24 CHAPTER 3: THE WORLD OF NMR: MAGNETS, RADIO WAVES, AND DETECTIVE WORK 26 A Slam Dunk for Enzymes 27 NMR Spectroscopists Use Tailor-Made Proteins 28 NMR Magic Is in the Magnets 29 The Many Dimensions of NMR 30 NMR Tunes in on Radio Waves 31 Spectroscopists Get NOESY for Structures 32 The Wiggling World of Proteins 32 Untangling Protein Folding 33 Student Snapshot: The Sweetest Puzzle 34 CHAPTER 4: STRUCTURE-BASED DRUG DESIGN: FROM THE COMPUTER TO THE CLINIC 36 The Life of an AIDS
    [Show full text]