Structural Insights Into Peptide Bond Formation
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Syntheses and Biological Activity of Sparsomycin and Analogs
SYNTHESES AND BIOLOGICAL ACTIVITY OF SPARSOMYCIN AND ANALOGS THE CHEMISTRY OF CHIRAL FUNCTIONALIZED SULFOXIDES AND SULTINES DERIVED FROM CYSTEINE ROB M.J. LISKAMP SYNTHESES AND BIOLOGICAL ACTIVITY OF SPARSOMYCIN AND ANALOGS THE CHEMISTRY OF CHIRAL FUNCTIONALIZED SULFOXIDES AND SULTINES DERIVED FROM CYSTEINE Promotor : Prof. Dr. R.J.F. Nivard Co-referent : Dr. H.C.J. Ottenheijm SYNTHESES AND BIOLOGICAL ACTIVITY OF SPARSOMYCIN AND ANALOGS THE CHEMISTRY OF CHIRAL FUNCTIONALIZED SULFOXIDES AND SULTINES DERIVED FROM CYSTEINE PROEFSCHRIFT TER VERKRIJGING VAN DE GRAAD VAN DOCTOR IN DE WISKUNDE EN NATUURWETENSCHAPPEN AAN DE KATHOLIEKE UNIVERSITEIT VAN NIJMEGEN OP GEZAG VAN DE RECTOR MAGNIFICUS PROF. DR. J.H.G.I. GIESBERS VOLGENS HET BESLUIT VAN HET COLLEGE VAN DEKANEN IN HET OPENBAAR TE VERDEDIGEN OP VRIJDAG 10 DECEMBER 1982 DES NAMIDDAGS OM 4 UUR DOOR ROBERTUS MATTHIAS JOSEPH LISKAMP GEBOREN TE NIJMEGEN NIJMEGEN 1982 Dit proefschrift vormt de neerslag van vier jaar wetenschappelijk onderzoek. Ik wil iedereen - en dat waren er zeer velen - bedanken, die hieraan gedurende die tijd door hun stimulerende discussie of door de feitelijke uitvoering deel hadden. Zij gaven mede richting en vorm, niet alleen organisch maar ook biochemisch/biologisch en fysisch chemisch, aan het verrichte onderzoek. Daarnaast wil ik hen bedanken die een bijdrage geleverd hebben aan de onmis bare technische uitvoering van het in dit proefschrift beschreven onderzoek. En tenslotte wil ik ook hen bedanken die aan de vormgeving van het proef schrift hun medewerking hebben verleend. Tekeningen : Wim van Luijn en de afdeling illustratie Type-werk : Dorine Hesselink-Balvert Afbeelding op de omslag: Een 'stacked plot' van een 2D-spin-echo correlated spectrum van synthetisch sparsomycine verzorgd door Wim Guijt This research was supported by the Netherlands Foundation for Chemical Research (SON) with financial aid from the Netherlands Organization for the Advancement of Pure Research (ZWO). -
The Ribosomal Peptidyl Transferase Center: Structure, Function, Evolution, Inhibition
Critical Reviews in Biochemistry and Molecular Biology, 40:285–311, 2005 Copyright c Taylor & Francis Inc. ! ISSN: 1040-9238 print / 1549-7798 online DOI: 10.1080/10409230500326334 The Ribosomal Peptidyl Transferase Center: Structure, Function, Evolution, Inhibition Norbert Polacek Innsbruck Biocenter, Division of ABSTRACT The ribosomal peptidyl transferase center (PTC) resides in the Genomics and RNomics, large ribosomal subunit and catalyzes the two principal chemical reactions of Innsbruck Medical University, protein synthesis: peptide bond formation and peptide release. The catalytic Innsbruck, Austria mechanisms employed and their inhibition by antibiotics have been in the Alexander S. Mankin focus of molecular and structural biologists for decades. With the elucidation Center for Pharmaceutical of atomic structures of the large ribosomal subunit at the dawn of the new Biotechnology, University of millennium, these questions gained a new level of molecular significance. The Illinois at Chicago, Chicago, crystallographic structures compellingly confirmed that peptidyl transferase is IL 60607, USA an RNA enzyme. This places the ribosome on the list of naturally occurring riboyzmes that outlived the transition from the pre-biotic RNA World to con- temporary biology. Biochemical, genetic and structural evidence highlight the role of the ribosome as an entropic catalyst that accelerates peptide bond for- mation primarily by substrate positioning. At the same time, peptide release should more strongly depend on chemical catalysis likely involving an rRNA group of the PTC. The PTC is characterized by the most pronounced accu- mulation of universally conserved rRNA nucleotides in the entire ribosome. Thus, it came as a surprise that recent findings revealed an unexpected high level of variation in the mode of antibiotic binding to the PTC of ribosomes from different organisms. -
How a Chemist Looks at RNA Thomas R
Angewandte Chemie DOI: 10.1002/anie.201205427 RNA Chemistry How a Chemist Looks at RNA Thomas R. Cech* 1989 chemical genetics · kinetics · RNA · thermo- dynamics I was passing through customs some time ago, returning from splicing reaction.[5] At the same time, it became increasingly London. The immigration officer, seemingly unsatisfied with clear that rRNA must have an active role in protein syn- my self-identification as “professor,” inquired about my thesis,[6] which was later confirmed in atomic detail by X-ray research area. “Molecular biology,” I answered; then added crystallography.[7] Evolution-in-a-test-tube experiments “ribonucleic acid,” certain this would convince him that I was showed that the potential versatility of RNA far exceeded harmless. the examples found in nature thus far,[8] adding credibility to At other times I identify myself as a biochemist, but the idea of a primordial “RNA World” where RNA served as almost never as just-plain chemist. This may seem a bit odd, both genetic material and as catalyst. given that all of my formal degrees (B.A. Grinnell College, The next rush of RNA discoveries concerned RNA as Ph.D. UC Berkeley) are in Chemistry, my first (and only) a regulator of gene expression. It had previously been thought faculty appointment has been in a Department of Chemistry, that most regulation was conducted by proteins that either and I teach General Chemistry to undergraduates. The repressed or activated gene transcription (the DNA!RNA opportunity to write something to help celebrate 125 years step) or regulated mRNA stability or translation (the RNA! of Angewandte Chemie has prompted me to organize some protein step). -
Dashawn Hickman
DaShawn Antwane Hickman 2816 Edgehill Road |Cleveland Heights, OH 44118 Phone: (203) 873-8344 |Email: [email protected] Education Case Western Reserve University, Cleveland, OH Doctor of Philosophy (Ph.D) expected May 2017 Doctor of Medicine (M.D.) expected May 2019 Yale University, New Haven, CT Bachelor of Science, Biomedical Engineering Awarded May 2009 A.C. Flora High School, Columbia, SC High School Diploma Awarded May 2005 International Baccalaureate Diploma Awarded May 2005 Research Department of Biomedical Engineering, Case Western Reserve University, Graduate Student Experience Cleveland, OH, May 2013-August 2015 § Principle Investigator: Erin Lavik, ScD § Synthesize polymer based hemostatic nanoparticles § Characterize nanoparticles using dynamic light scattering and ultra performance liquid chromatography § Validate efficacy and safety of treatments in rodent and porcine animal models § Investigate the immune response (CARPA) to hemostatic nanoparticles Department of Internal Medicine/Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Research Technician Little Rock, AR, Feb 2011-May 2011 § Principle Investigator: Jonathan Dranoff, MD § Perform functional and molecular studies on bile duct epithelia and portal fibroblast § Develop models examining the interaction of bile duct epithelia and portal fibroblast § Independent Literature Review § Present research in formal lab meetings Department of Internal Medicine/Digestive Diseases, Yale University, Postgraduate Associate New Haven, CT, July -
Yale University New Faculty Orientation Handbook Contents
Yale University New Faculty Orientation Handbook Contents 3 New Faculty Orientation Agenda 7 Welcome to Yale 9 New Faculty Orientation Participants 12 New Faculty Biographies & Headshots 32 Get the Facts! 41 Titles IV Policies at Yale 78 Teaching at Yale: An Introduction to the Yale Center for Teaching and Learning 91 Understanding Review, Promotion and Leaves 132 Yale Faculty Handbook: Full Document 134 Research & Teaching Resources: Concurrent Sessions 135 Session A: Using Yale Library Resources in Your Research & Teaching 138 Session B: Managing Grants, Contracts, & External Funding at Yale 167 Session C: Using Yale’s Collections in your Research & Teaching 176 Session D: Teaching, Learning and Research with Technology 179 Session E: Environmental Health & Safety in your Lab/Research 190 Office of Post Doctorial Affairs 193 TEAL Classroom Yale University New Faculty Orientation Agenda 2014-2015 New Faculty Member Orientation Academic Year 2014 – 15 Tuesday, August 19th 5:30 pm Welcome BBQ with Provost (New Faculty & Guests, Deans, and Chairs invited) 35 Hillhouse Avenue Ben Polak Provost of Yale University; William C. Brainard Professor of Economics and Management Wednesday, August 20th 8:00 am Registration and Breakfast Presidents Room, 2nd Floor of Memorial Hall 8:30 am Introductions & Overview of Agenda James Antony Associate Provost 8:45 am Welcome to Yale Peter Salovey President of Yale University; Chris Argyris Professor of Psychology 9:00 am Undergraduate and Graduate Students at Yale: An Overview Presidents Room, 2nd Floor, -
Fifth–Year Report
Fifth-Year Interim Report to the New England Association of Schools and Colleges Commission on Institutions of Higher Education Yale University New Haven, Connecticut August 15, 2014 Table of Contents Introduction . 1 Institutional Overview . 1 Responses to Areas Identified for Special Emphasis . 3 1. Financial Resources . 4 2. The West Campus . 6 3. Graduate Student Facilities & Campus Life . 9 4. Leadership and Faculty Diversity . 10 5. Assessment . .14 6. Committee on Yale College Education Follow-Up . 14 Standards: Changes since 2009 and Future Projections 1. Mission and Purpose . 15 2. Planning and Evaluation . 16 3. Organization and Governance . 20 4. The Academic Program. 22 5. Faculty. 28 6. Students . 30 7. Library and Information Resources . 32 8. Physical and Technological Resources . 35 9. Financial Resources . 37 10. Public Disclosure . 39 11. Integrity . 41 Assessment, Retention, and Student Success . 43 Plans for the Future. 59 INTRODUCTION Yale University’s 2014 Fifth-Year NEASC Interim Report offers the opportunity not only to reflect on changes since the 2009 Self Study, but also to consider the future. We address the six areas identified for special emphasis by the Commission on Institutions of Higher Education, discussing actions taken and making projections about what needs continued attention. We review the eleven CIHE Standards, reporting on significant changes since our 2009 evaluation as well as how Yale continues to meet the standards and projects future directions. In Standard Four, The Academic Program, we focus on the Faculty of Arts and Sciences, which teaches over two-thirds of Yale students and has the largest contingent of Yale faculty. -
COMMEMORATIVE LECTURE Structural Insights Into the Functions of the Large Ribosomal Subunit, a Major Antibiotic Target Thomas A
COMMEMORATIVE LECTURE Structural Insights into the Functions of the Large Ribosomal Subunit, a Major Antibiotic Target Thomas A. Steitz Investigator, Howard Hughes Medical Institute and Sterling Professor of Molecular Biophysics and Biochemistry, Yale University Professor of Chemistry, Yale University, New Haven, CT, USA (Received for publication on Ausust 25, 2007) Key words: Ribosome structure, RNA, antibiotics, protein synthesis, ribozyme Chairman (Prof. Yoshikazu Nakamura, Institute for Prof. Thomas A. Steitz, Department of Molecular Medical Science, University of Tokyo): Finally we will Biophysics and Biochemistry and Department of have a lecture by Prof. Thomas A. Steitz. He is the win- Chemistry, Yale University, and Howard Hughes ner of Keio Medical Science Prize. Already, he explained Medical Institute: It is a great pleasure to be here, and or talked about his personal history and therefore really I thank you so much for that kind introduction. As I said do not need to repeat the same thing; but briefly I would yesterday, it is always wonderful to come to Japan and like to introduce his career. He graduated in Chemistry visit. My son and I had a great breakfast this morning; a from Lawrence College,Wisconsin in 1962, and he fin- sushi breakfast at the fish dock,*1 the best sushi that I ished his PhD in biochemistry and molecular biology at ever had in my life; it is going to be hard to do this again, Harvard University. Then he started his professional ca- I have to say, back home. My son is out having a good reer path in Harvard University, the same department of time in Tokyo and I am here having to talk, so I am go- chemistry, and he also spent three years 1967-1970 in ing to have a good time too. -
Sparsomycin and Its Analogues
PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/113516 Please be advised that this information was generated on 2021-10-06 and may be subject to change. SPARSOMYCIN AND ITS ANALOGUES A preclinical study on novel anticancer drugs Promotores: Prof. Dr. D.J.Th. Wagener Prof. Dr. E. van der Kleijn Prof. Dr. H.C.J. Ottenheijm (V.U., Amsterdam) SPARSOMYCIN AND ITS ANALOGUES A preclinical study on novel anticancer drugs een wetenschappelijke proeve op het gebied van de geneeskunde en tandheelkunde PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Katholieke Universiteit te Nijmegen, volgens besluit van het college van decanen in het openbaar te verdedigen op dinsdag 7 juni 1988 des namiddags te 3.30 uur door Zbigniew Zylicz geboren op 13 juni 1955 te Wroclaw (Polen) Nijmegen, 1988 druk: reprografie faculteit der geneeskunde en tandheelkunde The investigations have been performed at the Department of Internal Medicine, Division of Medical Oncology, and the Department of Clinical Pharmacy, University Hospital Nijmegen, The Netherlands. These studies were supported by The Netherlands Cancer Foundation Queen Wilhelmina Fund (grant nr SNUKC-84-1) and Pharmachemie BV, Haarlem, The Netherlands. Pharmachemie BV, Haarlem, is also acknowledged for financial support of publication of this thesis. Yr3/V)ornm vr? тле/ г$и Abbreviat ions AUG - area under the plasma concentration versus time curve ARA-C - cytosine arabinoside CHO - Chinese hamster ovary cells CL-j, - creatinine clearance CL™ - non-renal clearance CLp - renal clearance С - steady state concentration D - dose dSm - deshydroxy-sparsomycin EdSm - ethyl-deshydroxy-sparsomycin 5-FU - 5-fluorouracil i.d. -
Synthesis and Biological Evaluation of Sparsomycin Analogues
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 1981 Synthesis and biological evaluation of sparsomycin analogues Scherer Preston Sanders Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Medicinal and Pharmaceutical Chemistry Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/5601 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. SYNTHESIS AND BIOLOGICAL EVALUATION OF SPARSOMYCIN ANALOGUES by Scherer Preston Sanders Duke B.S. , College of William and Mary , 1977 Thesis submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Department of Pharmaceutical Chemistry at the Medical College of Virginia, Virginia Commonwealth University Richmond , Virginia August , 1981 ii This thesis by Scherer Preston Sanders Duke is accepted in its present form as satisfying the thesis requirement for the degree of Doctor of Philosophy . Date : Approved: 1- l I � I · •.•..... ••... •..•.•...•• - TJl ':7 J. � · . •. [v:7. � !� t 9 r ! ..... /) · ....� . �J.) . (q.ft... · ... :r u.l'f . .�l t. I g 8-l........ · .. Cf4r,;2/., . 1'1.f1..... Approved : . Chairman , MCV Graduate Council; Dean , Schoo l of Basic Sciences iii Scherer Preston Sanders Duke 1981 All Rights Reserved iv ACKNOWLEDGMENTS I wish to thank the members of my graduate committee for overseeing this project and especially my advisor , Dr. Marvin R. Boots , for his guidance and encouragement throughout the course of this research and the preparation of this thesis. -
University Science Strategy Committee
University Science Strategy Committee Scott Strobel, PhD (Chair) Scott Strobel joined the Yale faculty in 1995 in the Department of Molecular Biophysics & Biochemistry (MB&B) where he served as department chair from 2006-09 and currently holds the Henry Ford II Professorship. Since 2011 he has served as vice president for West Campus planning & program development, and in July 2014 he took on additional responsibility as the inaugural deputy provost for teaching & learning. In this capacity, he will oversee the development of a comprehensive Yale Center for Teaching and Learning that will promote teaching excellence, foster improved student learning, and provide a clear pathway for teaching resources and support to Yale faculty, postdocs, graduate students, and undergraduate students. In 2006 and again in 2010, he was named a Howard Hughes Medical Institute (HHMI) Professor to promote efforts in undergraduate science education. With this award he instituted a program to explore microbial and chemical diversity in the world’s rainforests as a means to inspire undergraduate students in the sciences. He was awarded the Dylan Hixon Prize for Teaching Excellence in the Natural Sciences in 2004 and the Graduate Mentoring Award in the Sciences in 2007. He received his B.A. from Brigham Young University and his Ph.D. from the California Institute of Technology. His current research explores the chemical basis of RNA function and catalysis and hydrocarbon production by endophytic fungi. Daniel Alfonso Colón-Ramos, PhD Daniel Colón-Ramos was born and raised in Puerto Rico. He completed his B.A. at Harvard University, his PhD in the lab of Dr. -
Cell Cycle Phase Specificity of Antitumor Agentsl
[CANCER RESEARCH 32, 398-407, February 1972] Cell Cycle Phase Specificity of Antitumor Agentsl B. K. Bhuyan, L. G. Scheldt, and T. J. Fraser Research Laboratories, The Upjohn Company, Kalamazoo, Michigan 49001 SUMMARY correlating the biochemical effect of the drug to its lethal effect. For example, many drugs are maximally toxic to cells The sensitivity to drugs of synchronous and asynchronous at the G]-S boundary, and a correlation between the lethal populations of DON cells was studied. Agents that were and biochemical effects of the drug may help to delineate the cytotoxic at a specific phase of the cell cycle gave dose-survival biochemical reaction that triggers the cell across the Gi-S curves that decreased to a constant saturation value. DNA boundary, (b) They may help in designing combinations of synthesis inhibitors such as 1-0-D-arabinofuranosylcytosine, drugs on a rational basis. Thus, 2 drugs affecting the same 5-azacytidine, 5-hydroxy-2-formylpyridinethiosemicarbazone phase of the cell cycle would not give additive effects, if (NSC 107392), sodium camptothecin (NSC 100880), combined. 5-fluorodeoxyuridine, and pseudourea (NSC 56054) were Our studies were intended to determine the phase most cytotoxic to cells in the S phase. However, the DNA specificity of several clinically active agents and of agents with synthesis inhibitor, neocarzinostatin, was most cytotoxic to known biochemical activity. Parts of this study were reported cells in the G! phase. The protein synthesis inhibitors, previously (7). pactamycin and sparsomycin, were also most cytotoxic to cells in the S phase. Cells in the Gi-S border region were most MATERIALS AND METHODS sensitive to the RNA synthesis inhibitors, actinomycin D and nogalamycin, and to the alkylating agents, Cell Culture. -
The Ribosomal Peptidyl Transferase Center: Structure, Function, Evolution, Inhibition
Critical Reviews in Biochemistry and Molecular Biology, 40:285–311, 2005 Copyright c Taylor & Francis Inc. ISSN: 1040-9238 print / 1549-7798 online DOI: 10.1080/10409230500326334 The Ribosomal Peptidyl Transferase Center: Structure, Function, Evolution, Inhibition Norbert Polacek Innsbruck Biocenter, Division of ABSTRACT The ribosomal peptidyl transferase center (PTC) resides in the Genomics and RNomics, large ribosomal subunit and catalyzes the two principal chemical reactions of Innsbruck Medical University, protein synthesis: peptide bond formation and peptide release. The catalytic Innsbruck, Austria mechanisms employed and their inhibition by antibiotics have been in the Alexander S. Mankin focus of molecular and structural biologists for decades. With the elucidation Center for Pharmaceutical of atomic structures of the large ribosomal subunit at the dawn of the new Biotechnology, University of millennium, these questions gained a new level of molecular significance. The Illinois at Chicago, Chicago, crystallographic structures compellingly confirmed that peptidyl transferase is IL 60607, USA an RNA enzyme. This places the ribosome on the list of naturally occurring riboyzmes that outlived the transition from the pre-biotic RNA World to con- temporary biology. Biochemical, genetic and structural evidence highlight the role of the ribosome as an entropic catalyst that accelerates peptide bond for- mation primarily by substrate positioning. At the same time, peptide release should more strongly depend on chemical catalysis likely involving an rRNA group of the PTC. The PTC is characterized by the most pronounced accu- For personal use only. mulation of universally conserved rRNA nucleotides in the entire ribosome. Thus, it came as a surprise that recent findings revealed an unexpected high level of variation in the mode of antibiotic binding to the PTC of ribosomes from different organisms.