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Conference Program
 
Nucleosides, Nucleotides & Oligonucleotides
July 1-6, 2007
Salve Regina University
Newport, RI
Chair:
Jyoti Chattopadhyaya

Vice Chair:
Varsha Gandhi

DNA is the storehouse of genetic information. Genes are duplicated during each cell division (replication), and they are transcribed into the corresponding RNAs (transcription) before translation into the proteins that are required for cell function. RNA is subsequently processed so that the non-coding parts are removed (processing), and it is then transported out of the nucleus (transport). Outside of the nucleus, proteins are assembled, based upon the triplet code, at ribosomal sites in the translation process. This complex interplay requires constant interaction between proteins and many other cofactors. The goal of this Conference is to highlight our current understanding of the various chemical steps through the use of synthetic "Nucleosides, Nucleotides and Oligonucleotides" and their analogs in order to design new therapeutic, analytical and diagnostic agents. The usefulness of these synthetic compounds is enormous. Synthetic nucleosides and nucleotides and their analogs, for example, have found application as many remarkable antiviral and antitumor drugs which are used widely in the clinic against many deadly bacterial and viral infections and against malignant tumors. Many drugs approved by the FDA as antiviral/antitumor agents are nucleoside-based compounds. The mechanism of action of many such nucleoside/nucleotide based inhibitors is through interaction/inhibition with/of the target enzymes (novel mechanism-based inactivators). The use of oligonucleotides and their analogs is, on the other hand, constantly revealing new methods to alter and to monitor gene expression by means of antisense RNA or DNA, triplex DNA, ribozymes, RNAi, CpG immune modulatory oligonucleotides, DNA oxidative damage, gene repair, DNA chips, and by other approaches. The design and synthesis of oligonucleotides and their analogs have opened doors to the understanding of the mechanisms of action of these compounds as potential therapeutic agents, including their uptake, stability, in both prokaryotic and eukaryotic organisms, and in both in vitro and in vivo systems, leading to lowered toxicity and improved efficacy. Oligonucleotides with fluorescent dyes provide unique molecular probe systems that are useful for the detection of PCR products and nucleic acid hybridization as well as for sequencing. Many revolutionary concepts involving specifically designed RNA and DNA oligonucleotides with novel functions have been shown to be useful in target validation and as new analytical and therapeutic agents. In this respect, new emerging areas include the design of nanoprobes, sensors and many sensitive diagnostic tools for the detection of single nucleotide polymorphism, high affinity binding (aptamers), catalytic activity (ribozymes and deoxyribozymes) and combinations of binding and catalytic properties (aptazymes).

This very brief summary of the field demonstrates how important the synthetic chemistry of "Nucleosides, Nucleotides and Oligonucleotides" is in the exploration and understanding of life, and how this knowledge has been invaluable in the design of new analytical and therapeutic agents. This opportunity to communicate with each other and to learn from our individual ideas and experiments at this GRC will undoubtedly be of enormous value.


SUNDAY
2:00 pm - 11:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:35 pmWelcome / Introductory Comments by GRC Site Staff
7:35 pm - 9:20 pm Novel Mechanism-Based Inactivators
7:40 pm - 7:45 pmDiscussion Leader: Jyoti Chattopadhyaya (Uppsala Univ, Sweden)
7:45 pm - 8:35 pmKeynote Speaker: JoAnne Stubbe (MIT, USA)
"Gemzar inactivation of human and bacterial Ribonucleotide Reductases"
8:35 pm - 8:40 pmDiscussion
8:40 pm - 9:15 pmTomas Cihlar (Gilead Sciences, USA)
"Cyclic nucleoside phosphonates and their prodrugs as inhibitors of HIV: Discovery of GS-9131"
9:15 pm - 9:20 pmDiscussion
9:30 pm - 10:30 pmChair’s Reception
MONDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pm Designing function with Nucleoside and Nucleotide Chemistry (Chosen from the posters)
9:00 am - 9:05 amDiscussion Leader: Varsha Gandhi (MD Andersson cancer Ctr., Texas)
9:05 am - 9:15 amEric Brown (Northwestern Univ; USA)
"Determining the Ability of TiO2-Peptide Nucleic Acid-Nanocomposites to Image and Cleave Deleterious DNA"
9:15 am - 9:20 amDiscussion
9:20 am - 9:35 amZhen Huang (Georgia State University)
"Nucleotide Atom-specific Derivatization with Selenium for Structure and Function Studies of Nucleic Acids"
9:35 am - 9:40 amDiscussion
9:40 am - 9:55 amJonathan Watts (McGill University)
"Impact of 2'-F versus 2'-OH on the stability of arabinonucleic acid/RNA hybrids. Why such a large difference?"
9:55 am - 10:00 amDiscussion
10:00 amCoffee Break / Group Photo
10:25 am - 10:50 amFrank Seela (University Of Osnabrueck, Germany)
"The Copper-Catalyzed Cycloaddition (‘Click’ Reaction) Performed on DNA and their Constituents"
10:50 am - 10:55 amDiscussion
10:55 am - 11:20 amKrzysztof Pankiewicz (University of Minnesota Center for Drug Design)
"Dual Inhibition of IMPDH and Histone Deacetylases by Mycophenolic Hydroxamic Acids and its Mimics"
11:20 am - 11:25 amDiscussion
11:25 am - 11:50 amVirinder Parmar (University Of Delhi)
"Novel Biocatalytic Reactions on Carbohydrates and Nucleosides"
11:50 am - 11:55 amDiscussion
11:55 am - 12:25 pmJanez Plavec (National Institute Of Chemistry, Ljubliana, Slovenia)
"NMR studies on cation localization and dynamics within G-quadruplexes"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pm DNA/RNA Chemistry
7:30 pm - 7:40 pmDiscussion Leader: Akira Matsuda (Univ of Hokkaido , Japan)
7:40 pm - 8:20 pmChad Mirkin (North Western Univ, USA)
"Non-enzymatic approaches to amplification in biological detection systems"
8:20 pm - 8:25 pmDiscussion
8:25 pm - 9:05 pmMarv Caruthers (Colorado Univ, USA)
"New Methods for Synthesizing RNA/DNA and Borane Phosphonate DNA"
9:05 pm - 9:10 pmDiscussion
9:10 pm - 9:25 pmYogesh Sanghvi (Rasayan Inc)
"Chemo-, Regio- and Stereoselective Syntheses of Protected Nucleosides and Carbohydrates Using Biocatalytic Processes"
9:25 pm - 9:30 pmDiscussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pm Functional Oligos
9:00 am - 9:10 amDiscussion Leader: Oliver Seitz (Humboldt University Berlin)
9:10 am - 9:55 amNaoki Sugimoto (Konan Univeristy, Japan)
"Design and Development of Functional Molecules Based on Nucleic Acids"
9:55 am - 10:00 amDiscussion
10:00 amCoffee Break
10:30 am - 11:15 amKevin Weeks (The University of North Carolina at Chapel Hill, USA)
"Exploiting 2’-ribose chemistry for high-throughput RNA structure analysis"
11:15 am - 11:20 amDiscussion
11:20 am - 11:40 amEriks Rozners (Northeastern University)
"Synthesis and Properties of Nonionic RNA Analogues"
11:40 am - 11:45 amDiscussion
11:45 am - 12:05 pmOliver Seitz (Humboldt University Berlin)
"Signal Amplification By DNA-Catalyzed Reactions"
12:05 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmOles Plashkevych (Uppsala University)
"Molecular Structure of 10-23 DNAzyme and mechanism of its action"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pm DNA/RNA Interactions
7:30 pm - 7:40 pmDiscussion Leader: Frank Seela (University Of Osnabrueck, Germany)
7:40 pm - 8:15 pmEric Kool (Stanford Univ, USA)
"Chemistry of Information Transfer in Natural and Designed Genetic Systems"
8:15 pm - 8:20 pmDiscussion
8:20 pm - 8:55 pmPiet Herdiwijn (Rega Institute, Belgium)
"Synthetic biology using polymerases"
8:55 pm - 9:00 pmDiscussion
9:00 pm - 9:25 pmZhen Xi (Nankai Univ, China)
"Recognition of non-Watson-Crick structure and its application"
9:25 pm - 9:30 pmDiscussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pm DNA Repair
9:00 am - 9:05 amDiscussion Leader: Chris Meier (University of Hamburg)
9:05 am - 9:55 amJacqueline Barton (California Institute of Technology, USA)
"DNA Charge Transport for DNA Repair"
9:55 am - 10:00 amDiscussion
10:00 amCoffee Break
10:30 am - 11:15 amThomas Carell (Univ of Meunchen, Germany)
"Nucleosides for the Investigation of DNA Repair and Replication on an Atomic Level"
11:15 am - 11:20 amDiscussion
11:20 am - 11:40 amWojciech Stec (Polish Academy Of Sciences)
"Stereochemistry Of P-N Bond Cleavage By Hint Protein"
11:40 am - 11:45 amDiscussion
11:45 am - 12:05 pmKen Douglas (University of Manchester, UK)
"Beyond FRET: Single Base Pair-Resolution for Nucleic Acid Detection based on Target-Assembled Exciplexes"
12:05 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmMingxia Huang (University Of Colorado Health Sciences Ctr)
"Control Of dNTP Synthesis By The Cell Cycle And DNA Damage Checkpoint"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pm Conformationally-Constrained Nucleosides
7:30 pm - 7:40 pmDiscussion Leader: Victor Marquez (NCI, Bethesda)
7:40 pm - 8:15 pmJesper Wengel (Univ of Southern Denmark, Denmark)
"LNA (Locked Nucleic Acid) - Key Molecules Towards Realizing Gene Silencing Drugs"
8:15 pm - 8:20 pmDiscussion
8:20 pm - 8:50 pmVictor E. Marquez (Center for Cancer Research, National Cancer Institute-Frederick, USA
"The Properties of Locked Methanocarba Nucleosides in Biochemistry, Biotechnology and Medicinal Chemistry"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:25 pmLi He Zhang (Peking University)
"Studies on Cyclic Nucleotides and Modified Oligonucleotides"
9:25 pm - 9:30 pmDiscussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pm RNA targeting & Delivery
9:00 am - 9:05 amDiscussion Leader: Donna Shewac (University of Michigan Medical School)
9:05 am - 9:40 amMano Manoharan (Alnylam; USA)
"In vivo Delivery of Chemically Modified siRNAs"
9:40 am - 9:45 amDiscussion
9:45 am - 9:55 amPatrick Hrdlicka (University Of Idaho)
"Intercalator-Functionalized Nucleic Acids as Emerging Tools for Targeting of Double Stranded DNA"
9:55 am - 10:00 amDiscussion
10:00 amCoffee Break
10:30 am - 11:05 amAlan Gewirtz (University of Pennsylvania School of Medicine, USA)
"Surprising differences between antisense DNA and siRNA in mRNA target site preferences and cleavage efficiency"
11:05 am - 11:10 amDiscussion
11:10 am - 11:45 amSudhir Agrawal (Idera Pharma, USA)
"Synthetic DNA and RNA as agonist and antagonist of Toll like receptors: Therapeutic Applications"
11:45 am - 12:00 pmDiscussion
12:00 pm - 12:25 pmBarbara Nawrot (Polish Academy Of Sciences)
"Model For The Metal Binding Site Of Deoxyribozyme 10-23"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
(Nominations for the next Vice Chair(s); Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair(s))
7:30 pm - 9:30 pm Novel Nucleoside and Nucleoside-Prodrug Inhibitors and Purine Metabolism
7:30 pm - 7:40 pmDiscussion Leader: Staffan Eriksson (Swedish University of Agricultural Science)
7:40 pm - 8:20 pmDavid B. Olsen (Merck & Co., Inc)
"Discovery of Potent and Selective HCV Antiviral Nucleoside Analogs: SAR/Lessons Learned and Resistance Analysis"
8:20 pm - 8:25 pmDiscussion
8:25 pm - 9:05 pmVern Schramm (Albert Einstein College of Medicine, NY)
"Specificity and Transition State Analogues in Purine Metabolism"
9:05 pm - 9:10 pmDiscussion
9:10 pm - 9:25 pmStaffan Eriksson (Swedish University Of Agricultural Sciences)
"Predicting efficacy and toxicity of nucleoside analogs by in vitro tests with nucleoside and nucleotide kinases"
9:25 pm - 9:30 pmDiscussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

 
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