Search results for "rational design"
showing 3 items of 63 documents
Myotonic dystrophy: candidate small molecule therapeutics
2017
Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene. Mutant DMPK transcripts are toxic and alter gene expression at several levels. Chiefly, the secondary structure formed by CUGs has a strong propensity to capture and retain proteins, like those of the muscleblind-like (MBNL) family. Sequestered MBNL proteins cannot then fulfill their normal functions. Many therapeutic approaches have been explored to reverse these pathological consequences. Here, we review the myriad of small molecules that have been proposed for DM1, including examples obtained from computational rational …
Improvements in Rational Design Strategies of Inulin Derivative Polycation for siRNA Delivery.
2016
The advances of short interfering RNA (siRNA)-mediated therapy provide a powerful option for the treatment of many diseases, including cancer, by silencing the expression of targeted genes involved in the progression of the pathology. On this regard, a new pH-responsive polycation derived from inulin, Inulin-g-imidazole-g-diethylenetriamine (INU-IMI-DETA), was designed and employed to produce INU-IMI-DETA/siRNA "Inulin COmplex Nanoaggregates" (ICONs). The experimental results showed that INU-IMI-DETA exhibited strong cationic characteristics and high solubility in the pH range 3-5 and self-aggregation triggered by pH increase and physiological salt concentration. INU-IMI-DETA showed as well…
Evidence of Weak Halogen Bonding: New Insights on Itraconazole and its Succinic Acid Cocrystal
2012
Exact knowledge of the crystal structure of drugs and lead compounds plays a significant role in the fields of crystal engineering, docking, computational modeling (drug–receptor interactions), and rational design of potent drugs in pharmaceutical chemistry. The succinic acid cocrystal of the systemic antifungal drug, itraconazole, reported by Remenar et al. (J. Am. Chem. Soc.2003, 125, 8456–8457) (CSD: IKEQEU), represents one of the classical examples displaying a molecular fitting mechanism in the solid state. In this work, we disclose the X-ray single-crystal structure of the cis-itraconazole–succinic acid (2:1) cocrystal and found that it differs slightly from the previously reported st…