Brief Summary of the Second Year’s Research Sample Clauses

Brief Summary of the Second Year’s Research. The two specific aims were: Rational design and synthesis of new readthrough drugs (Aim #1); Chemical modification of NBs for improved cell permeability and bioavailability (Aim #2). The main achievements include: (1) We have generated a new series of pseudodisaccharides NB154 (exhibits unsaturation on ring I) and NB153 (6’,7’-chiral diol) by rational design strategy (employing the docking of NBs into our solved x-ray structures of AGs bound to the eukaryotic A-site rRNA oligonucleotide model) and demonstrated their improved activity in comparison to their parent compounds. Encouraged, the pseudo-disaccharide NB153 was used as a scaffold for the generation of two pseudo-trisaccharide structures NB156 and NB157, which then subsequently tested for a series of biological tests. Both were found significantly better than their parent structures NB74 (for NB156) and NB124 (for NB157). Thus, by using rational design approach we were able for the first time to provide the validation of this design strategy which provided significant activity improvement in comparison to the previous lead structures. In addition, the pseudo-disaccharide NB154 was used as a scaffold for the generation of the simplest pseudo-trisaccharide structure NB158, which again proved to be better than its parent NB30.
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