PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

实际样本调查统计学：非简单随机样本和赋值数据

在社会和商业等调查中所采用的样本通常并不如人们想象的那么随机，这种非随机性可能会影响由调查数据中得出的结论。     

The structure-antimicrobial relation of depsipeptides

Zusammenfassung Die Beziehungen zwischen Struktur und antimikrobieller Aktivität in der Reihe der Depsipeptide wurden untersucht. Cyclotetradepsipeptide sind praktisch inaktiv. Die grösste Aktivität besitzen die Cyclohexadepsipeptide mit regulärer Oxy- und Aminosäurensequenz. Eine weitere Vergrösserung des Depsipeptidringes führt zu einem Abfall der biologischen Aktivität. Cyclohexadepsipeptide mit irregulärer Oxy- und Aminosäurensequenz sind völlig inaktiv.

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Communication XXVII in the SeriesStudies in Depsipeptide Chemistry.     

The effect of antamanide and perhydroantamanide on the permeability of model and biological membranes

Zusammenfassung Untersuchungen mit Antamanid und Perhydroantamanid deuten darauf hin, dass für letzteres die Beeinflussung des Transportes von Na⁺- und K⁺-Ionen durch Membranen von Bedeutung sein kann.     

Mass spectrometric determination of the amino acid sequence in cystine- and cysteine-containing peptides

, - , , S-- S- .     

Topochemical approach to the structure-activity relation. Retroenantio-Gly5,10-gramicidin S

, . , -Gly^5,10- , Gly^5,10- .