Synthesis, structure, and activity of hybridization probes and immunostimulatory DNA

Autori

• Amritraj Patra

Parametri

• Libri di testo
• Libri di testo universitari

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This doctoral thesis presents findings from two projects involving synthetic oligonucleotides designed for studying their properties as hybridization probes and immunostimulatory agents. The first part examines oligonucleotides with molecular caps that enhance fidelity for hybridization probes. The research elucidates the duplex-stabilizing effect of an anthraquinonyl (AQ) residue at the 2'-position of a 3'-terminal 2'-amino-2'-deoxyuridine through high-resolution two-dimensional NMR and restrained molecular dynamics. The three-dimensional structure of (ACGCGU-AQ)2 indicates that the anthraquinone disrupts the terminal A:U base pair while capping the penultimate G:C base. A "composite cap" was designed to enable the anthraquinone to bridge terminal base pairs, with the uridine residue sealing them off from the minor groove. This composite cap emerged as the most effective duplex-stabilizing cap for 3'-termini of DNA hybridization probes, enhancing affinity and base pairing selectivity with complementary DNA and RNA strands. The second part investigates oligonucleotides that stimulate the innate immune system, focusing on those with a phosphodiester backbone and the core sequence 5'-GACGTT-3'. These oligonucleotides form higher ordered structures believed to enhance immunostimulation by improving cellular uptake and receptor recognition. The structures of the known immunostimulatory DNA eicosamer and its variants were analyzed

Lingua: Inglese

Pubblicato: 2009

(In brossura)