RNA Kissing-Loop Interactions Supported by Bifacial Peptide Nucleic Acid
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Design of Nucleic Acid Strands with Long Low-Barrier Folding Pathways
Nat Comput DOI 10.1007/s11047-016-9587-9 Design of nucleic acid strands with long low-barrier folding pathways Anne Condon1 · Bonnie Kirkpatrick2 · Ján Maˇnuch1 © The Author(s) 2017. This article is published with open access at Springerlink.com Abstract A major goal of natural computing is to design fully developed, that exploit base pairing interactions of biomolecules, such as nucleic acid sequences, that can be nucleic acids. Prominent examples include DNA strand dis- used to perform computations. We design sequences of placement systems (DSDs) (Seelig et al. 2006) and RNA nucleic acids that are “guaranteed” to have long folding origami systems (Geary and Andersen 2014). Our work here pathways relative to their length. This particular sequences is motivated by the goal of computing with a single RNA with high probability follow low-barrier folding pathways sequence as the nucleic acids of the sequence interact with that visit a large number of distinct structures. Long fold- each other. ing pathways are interesting, because they demonstrate that RNA sequences form folded structures in which pairs of natural computing can potentially support long and com- nucleic acids biochemically bond to each other. These bonds plex computations. Formally, we provide the first scalable change the physical energy of the sequence, and a given designs of molecules whose low-barrier folding pathways, sequence prefers to assume low-energy folded structures. with respect to a simple, stacked pair energy model, grow Folding is a dynamic process, constrained by kinetics, dur- superlinearly with the molecule length, but for which all sig- ing which an RNA sequence will move through a sequence nificantly shorter alternative folding pathways have an energy of structures with each differing from the previous one by barrier that is 2 − times that of the low-barrier pathway for the addition or removal of a single base pair. -
Algorithms for Nucleic Acid Sequence Design
Algorithms for Nucleic Acid Sequence Design Thesis by Joseph N. Zadeh In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy California Institute of Technology Pasadena, California 2010 (Defended December 8, 2009) ii © 2010 Joseph N. Zadeh All Rights Reserved iii Acknowledgements First and foremost, I thank Professor Niles Pierce for his mentorship and dedication to this work. He always goes to great lengths to make time for each member of his research group and ensures we have the best resources available. Professor Pierce has fostered a creative environment of learning, discussion, and curiosity with a particular emphasis on quality. I am grateful for the tremendously positive influence he has had on my life. I am fortunate to have had access to Professor Erik Winfree and his group. They have been very helpful in pushing the limits of our software and providing fun test cases. I am also honored to have two other distinguished researchers on my thesis committee: Stephen Mayo and Paul Rothemund. All of the work presented in this thesis is the result of collaboration with extremely talented individuals. Brian Wolfe and I codeveloped the multiobjective design algorithm (Chapter 3). Brian has also been instru- mental in finessing details of the single-complex algorithm (Chapter 2) and contributing to the parallelization of NUPACK’s core routines. I would also like to thank Conrad Steenberg, the NUPACK software engineer (Chapter 4), who has significantly improved the performance of the site and developed robust secondary structure drawing code. Another codeveloper on NUPACK, Justin Bois, has been a good friend, mentor, and reliable coding partner. -
Peptide Nucleic Acids, Morpholinos and Related Antisense Biomolecules
MEDICAL INTELLIGENCE UNIT Peptide Nucleic Acids, Morpholinos and Related Antisense Biomolecules Christopher G. Janson, M.D. Departments of Neurosurgery, Neurology and Molecular Genetics Cell and Gene Therapy Center UMDNJ-Robert Wood Johnson Medical School Camden, New Jersey, U.S.A. Matthew J. During, M.D., ScD. Department of Molecular Medicine and Pathology University of Auckland Auckland, New Zealand LANDES BIOSCIENCE / EUREKAH.COM KLUWER ACADEMIC / PLENUM PUBLISHERS GEORGETOWN, TEXAS NEW YORK, NEW YORK USA U.SA PEPTIDE NUCLEIC ACIDS, MORPHOLINOS AND RELATED ANTISENSE BIOMOLECULES Medical Intelligence Unit Landes Bioscience / Eurekah.com Kluwer Academic / Plenum Publishers Copyright ©2006 Eurekah.com and Kluwer Academic / Plenum Publishers All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher, vdth the exception of any material supplied specifically for the purpose of being entered and executed on a computer system; for exclusive use by the Purchaser of the work. Printed in the U.S.A. Kluwer Academic / Plenum PubHshers, 233 Spring Street, New York, New York, U.S.A. 10013 http ://www.wkap .nl/ Please address all inquiries to the Publishers: Landes Bioscience / Eurekah.com, 810 South Church Street, Georgetown, Texas, U.S.A. 78626 Phone: 512/ 863 7762; FAX: 512/ 863 0081 http ://v^^ww.eurekah. com http://www.landesbioscience.com Peptide -
(12) Patent Application Publication (10) Pub. No.: US 2013/0203610 A1 Meller Et Al
US 20130203610A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0203610 A1 Meller et al. (43) Pub. Date: Aug. 8, 2013 (54) TOOLS AND METHOD FOR NANOPORES Related U.S. Application Data UNZIPPING-DEPENDENT NUCLECACID (60) Provisional application No. 61/318,872, filed on Mar. SEQUENCING 30, 2010. (75) Inventors: Amit Meller, Brookline, MA (US); Alon Publication Classification Singer, Brighton, MA (US) (51) Int. Cl. (73) Assignee: TRUSTEES OF BOSTON CI2O I/68 (2006.01) UNIVERSITY, Boston, MA (US) (52) U.S. Cl. CPC .................................... CI2O I/6874 (2013.01) (21) Appl. No.: 13/638,455 USPC ................................................. 506/6:506/16 (57) ABSTRACT (22) PCT Filed: Mar. 30, 2011 Provided herein is a library that comprises a plurality of molecular beacons (MBs), each MB having a detectable (86). PCT No.: PCT/US2O11AO3O430 label, a detectable label blocker and a modifier group. The S371 (c)(1), library is used in conjunction with nanopore unzipping-de (2), (4) Date: Apr. 17, 2013 pendent sequencing of nucleic acids. Patent Application Publication Aug. 8, 2013 Sheet 1 of 18 US 2013/020361.0 A1 . N s Patent Application Publication Aug. 8, 2013 Sheet 2 of 18 US 2013/020361.0 A1 I’9IAI ::::::::::: Dº3.modoueN Patent Application Publication Aug. 8, 2013 Sheet 3 of 18 US 2013/020361.0 A1 Z’9IAI ~~~~~~~~~);........ Patent Application Publication Aug. 8, 2013 Sheet 4 of 18 US 2013/020361.0 A1 s :·.{-zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz iii. 9 iii.338 lii &S Patent Application Publication Aug. 8, 2013 Sheet 5 of 18 US 2013/020361.0 A1 s r Patent Application Publication Aug. -
Peptide Analogue of Glycol Nucleic Acid†
Communications to the Editor Bull. Korean Chem. Soc. 2011, Vol. 32, No. 8 2863 DOI 10.5012/bkcs.2011.32.8.2863 γ3PNA: Peptide Analogue of Glycol Nucleic Acid† Taedong Ok, Joohee Lee, and Hee-Seung Lee* Molecular-Level Interface Research Center, Department of Chemistry, KAIST, Daejeon 305-701 *E-mail: [email protected] Received February 7, 2011, Accepted February 9, 2011 Key Words : Peptide nucleic acids, GNA In the research of the chemical etiology of nucleic acid chemical yield were obtained with Mmt for γ3C and γ3G, Boc structure, the studies from Eschenmoser group1 and Nielsen for γ3A, respectively. In addition, the order of reactions at the group2 have demonstrated that the Watson-Crick base pairing initial steps turned out to be important for efficient synthesis. can be supported by various backbone derivatives. Inspired by For example, in case of γ3C, the protection of the amino groups the groundbreaking results, other researchers have devoted should be prior to the substitution reaction, whereas the other their attention to finding artificial nucleic acids that can form route worked better for the purine monomers (γ3A and γ3G). duplexes, in which both synthetic accessibility and new The detailed synthetic procedures are summarized in characteristics for potential therapeutic (or diagnostic) use are Scheme 1. The common intermediate bromide 1 was easily desirable aims.3 In this context, GNA (glycol nucleic acid, prepared from (S)-epichlorohydrin (> 99%ee) in three steps Figure 1A) is a promising artificial nucleic acid because it is (34% overall yield).6,7 For the synthesis of γ3A, the bromide 1 structurally very simple with a high atom economy and was reacted with unprotected adenine base in the presence of forms a duplex by Watson-Crick base pairing.4 sodium hydride in DMF for 48 hr at room temperature. -
Significance and Implications of Vitamin B-12 Reaction Shema- ETH ZURICH VARIANT: Mechanisms and Insights
Taylor University Pillars at Taylor University Student Scholarship: Chemistry Chemistry and Biochemistry Fall 2019 Significance and Implications of Vitamin B-12 Reaction Shema- ETH ZURICH VARIANT: Mechanisms and Insights David Joshua Ferguson Follow this and additional works at: https://pillars.taylor.edu/chemistry-student Part of the Analytical Chemistry Commons, Inorganic Chemistry Commons, Organic Chemistry Commons, Other Chemistry Commons, and the Physical Chemistry Commons CHEMISTRY THESIS SIGNIFICANCE AND IMPLICATIONS OF VITAMIN B-12 REACTION SCHEMA- ETH ZURICH VARIANT: MECHANISMS AND INSIGHTS DAVID JOSHUA FERGUSON 2019 2 Table of Contents: Chapter 1 6 Chapter 2 17 Chapter 3 40 Chapter 4 59 Chapter 5 82 Chapter 6 118 Chapter 7 122 Appendix References 3 Chapter 1 A. INTRODUCTION. Vitamin B-12 otherwise known as cyanocobalamin is a compound with synthetic elegance. Considering how it is composed of an aromatic macrocyclic corrin there are key features of this molecule that are observed either in its synthesis of in the biochemical reactions it plays a role in whether they be isomerization reactions or transfer reactions. In this paper the focus for the discussion will be on the history, chemical significance and total synthesis of vitamin B12. Even more so the paper will be concentrated one of the two variants of the vitamin B-12 synthesis, namely the ETH Zurich variant spearheaded by Albert Eschenmoser.Examining the structure as a whole it is observed that a large portion of the vitamin B12 is a corrin structure with a cobalt ion in the center of the macrocyclic part, and that same cobalt ion has cyanide ligands. -
Virus Research Frameshifting RNA Pseudoknots
Virus Research 139 (2009) 193–208 Contents lists available at ScienceDirect Virus Research journal homepage: www.elsevier.com/locate/virusres Frameshifting RNA pseudoknots: Structure and mechanism David P. Giedroc a,∗, Peter V. Cornish b,∗∗ a Department of Chemistry, Indiana University, 212 S. Hawthorne Drive, Bloomington, IN 47405-7102, USA b Department of Physics, University of Illinois at Urbana-Champaign, 1110 W. Green Street, Urbana, IL 61801-3080, USA article info abstract Article history: Programmed ribosomal frameshifting (PRF) is one of the multiple translational recoding processes that Available online 25 July 2008 fundamentally alters triplet decoding of the messenger RNA by the elongating ribosome. The ability of the ribosome to change translational reading frames in the −1 direction (−1 PRF) is employed by many Keywords: positive strand RNA viruses, including economically important plant viruses and many human pathogens, Pseudoknot such as retroviruses, e.g., HIV-1, and coronaviruses, e.g., the causative agent of severe acute respiratory Ribosomal recoding syndrome (SARS), in order to properly express their genomes. −1 PRF is programmed by a bipartite signal Frameshifting embedded in the mRNA and includes a heptanucleotide “slip site” over which the paused ribosome “backs Translational regulation HIV-1 up” by one nucleotide, and a downstream stimulatory element, either an RNA pseudoknot or a very stable Luteovirus RNA stem–loop. These two elements are separated by six to eight nucleotides, a distance that places the NMR solution structure 5 edge of the downstream stimulatory element in direct contact with the mRNA entry channel of the Cryo-electron microscopy 30S ribosomal subunit. The precise mechanism by which the downstream RNA stimulates −1 PRF by the translocating ribosome remains unclear. -
Transmissible Familial Creutzfeldt-Jakob Disease
Proc. Natl. Acad. Sci. USA Vol. 88, pp. 10926-10930, December 1991 Medical Sciences Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene (amyloid precursor protein/prion protein) LEV G. GOLDFARB*, PAUL BROWN*, W. RICHARD MCCOMBIEt, DMITRY GOLDGABERt, GARY D. SWERGOLD§, PETER R. WILLS¶, LARISA CERVENAKOVAII, HENRY BARON**, C. J. GIBBS, JR.*, AND D. CARLETON GAIDUSEK* *Laboratory of Central Nervous System Studies, and tSection of Receptor Biochemistry and Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; 4Department of Psychiatry, State University of New York, Stony Brook, NY; §Laboratory of Biochemistry, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; IDepartment of Physics, University of Auckland, New Zealand; Institute of Preventive and Clinical Medicine, Bratislava, Czechoslovakia; and **Searle Pharmaceuticals, Paris, France Contributed by D. Carleton Gajdusek, September 6, 1991 ABSTRACT The PRNP gene, encoding the amyloid pre- MATERIALS AND METHODS cursor protein that is involved in centrally Creutzfeldt-Jakob The Tested Population. A total of 535 individuals were disease (CJD), has an unstable region of five variant tandem screened for extra repeats in the PRNP gene: 117 patients octapeptide coding repeats between codons 51 and 91. We with spongiform encephalopathies (including 60 familial cas- screened a total of 535 individuals for the presence of extra es); 159 first-degree relatives ofpatients with familial spongi- repeats in this region, including patients with sporadic and form encephalopathies; 39 patients with other neurological familial forms ofspongiform encephalopathy, members oftheir diseases; 16 patients with non-neurological diseases; and 204 families, other neurological and non-neurological patients, and normal controls. -
A Global Sampling Approach to Designing and Reengineering RNA
i “rnaensign” — 2017/7/1 — 22:02 — page 1 — #1 i i i Published online ?? Nucleic Acids Research, ??, Vol. ??, No. ?? 1–11 doi:10.1093/nar/gkn000 Aglobalsamplingapproachtodesigningandreengineering RNA secondary structures 1,2, 1, 3 1 1 Alex Levin ⇤,MieszkoLis ⇤,YannPonty ,CharlesW.O’Donnell ,SrinivasDevadas , 1,2, 1,2,4, Bonnie Berger †,J´erˆomeWaldisp¨uhl † 1 Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA. and 2 Department of Mathematics, MIT, Cambridge, MA 02139, USA. and 3 Laboratoire d’Informatique, Ecole´ Polytechnique, Palaiseau, France. and 4 School of Computer Science, McGill University, Montreal, QC H2A 3A7, Canada. Received ??; Revised ??; Accepted ?? ABSTRACT mechanisms (1), reprogramming cellular behavior (2), and designing logic circuits (3). The development of algorithms for designing artificial Here, we aim to design RNA sequences that fold into RNA sequences that fold into specific secondary structures specific secondary structures (a.k.a. inverse folding). Even has many potential biomedical and synthetic biology in this case, efficient computational formulations remain applications. To date, this problem remains computationally difficult, with no exact solutions known. Instead, the solutions difficult, and current strategies to address it resort available today rely on local search strategies and heuristics. to heuristics and stochastic search techniques. The Indeed, the computational difficulty of the RNA design most popular methods consist of two steps: First a problem was proven by M. Schnall-Levin et al. (4). random seed sequence is generated; next, this seed is One of the first and most widely known programs for progressively modified (i.e. mutated) to adopt the desired the RNA inverse folding problem is RNAinverse (5). -
The Architecture of the Protein Domain Universe
The architecture of the protein domain universe Nikolay V. Dokholyan Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599 ABSTRACT Understanding the design of the universe of protein structures may provide insights into protein evolution. We study the architecture of the protein domain universe, which has been found to poses peculiar scale-free properties (Dokholyan et al., Proc. Natl. Acad. Sci. USA 99: 14132-14136 (2002)). We examine the origin of these scale-free properties of the graph of protein domain structures (PDUG) and determine that that the PDUG is not modular, i.e. it does not consist of modules with uniform properties. Instead, we find the PDUG to be self-similar at all scales. We further characterize the PDUG architecture by studying the properties of the hub nodes that are responsible for the scale-free connectivity of the PDUG. We introduce a measure of the betweenness centrality of protein domains in the PDUG and find a power-law distribution of the betweenness centrality values. The scale-free distribution of hubs in the protein universe suggests that a set of specific statistical mechanics models, such as the self-organized criticality model, can potentially identify the principal driving forces of molecular evolution. We also find a gatekeeper protein domain, removal of which partitions the largest cluster into two large sub- clusters. We suggest that the loss of such gatekeeper protein domains in the course of evolution is responsible for the creation of new fold families. INTRODUCTION The principles of molecular evolution remain elusive despite fundamental breakthroughs on the theoretical front 1-5 and a growing amount of genomic and proteomic data, over 23,000 solved protein structures 6 and protein functional annotations 7-9. -
3.1.4 Droplet-Based Microfluidics
Rodriguez Garcia, Marc (2016) Engineering the transition from non-living to living matter. PhD thesis. https://theses.gla.ac.uk/7605/ Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] Engineering the transition from non-living to living matter Marc Rodríguez Garcia A thesis submitted to the University of Glasgow for the degree of Doctor of Philosophy School of Chemistry College of Science and Engineering August 2016 A tota la meva família, per haver-me ajudat a arribar fins aquí. Però sobretot als meus pares, per estar tant a prop malgrat la distància. I en especial a la Nuria, per ser el motiu que em fa tirar endavant. “The good thing about science is that it's true whether or not you believe in it.” -Neil deGrasse Tyson Acknowledgements 1 Acknowledgements This project was carried out between September 2012 and June 2016 in the group of Prof Leroy Cronin in the School of Chemistry at the University of Glasgow. I have received much help and support from many colleagues and friends. -
Chapter 23 Nucleic Acids
7-9/99 Neuman Chapter 23 Chapter 23 Nucleic Acids from Organic Chemistry by Robert C. Neuman, Jr. Professor of Chemistry, emeritus University of California, Riverside [email protected] <http://web.chem.ucsb.edu/~neuman/orgchembyneuman/> Chapter Outline of the Book ************************************************************************************** I. Foundations 1. Organic Molecules and Chemical Bonding 2. Alkanes and Cycloalkanes 3. Haloalkanes, Alcohols, Ethers, and Amines 4. Stereochemistry 5. Organic Spectrometry II. Reactions, Mechanisms, Multiple Bonds 6. Organic Reactions *(Not yet Posted) 7. Reactions of Haloalkanes, Alcohols, and Amines. Nucleophilic Substitution 8. Alkenes and Alkynes 9. Formation of Alkenes and Alkynes. Elimination Reactions 10. Alkenes and Alkynes. Addition Reactions 11. Free Radical Addition and Substitution Reactions III. Conjugation, Electronic Effects, Carbonyl Groups 12. Conjugated and Aromatic Molecules 13. Carbonyl Compounds. Ketones, Aldehydes, and Carboxylic Acids 14. Substituent Effects 15. Carbonyl Compounds. Esters, Amides, and Related Molecules IV. Carbonyl and Pericyclic Reactions and Mechanisms 16. Carbonyl Compounds. Addition and Substitution Reactions 17. Oxidation and Reduction Reactions 18. Reactions of Enolate Ions and Enols 19. Cyclization and Pericyclic Reactions *(Not yet Posted) V. Bioorganic Compounds 20. Carbohydrates 21. Lipids 22. Peptides, Proteins, and α−Amino Acids 23. Nucleic Acids **************************************************************************************