Publications by authors named "Daniel D Peebles"

Purpose: A family of 17 new nucleophilic-polyamine and aminothiol structures was designed and synthesized to identify new topical or systemic radioprotectors with acceptable mammalian toxicity profiles. design elements included: (i) Length and charge of the DNA-interacting, alkylamine backbone, (ii) nucleophilicity of the reactive oxygen species (ROS)-scavenging group, and (iii) non-toxic drug concentration achievable in animal tissues.

Materials And Methods: Mouse maximum tolerated doses (MTD) were determined by increasing intraperitoneal (IP) doses.

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To identify new aminothiol radioprotectors that are active when applied topically and have fewer side effects when administered systemically, a new family of aminothiol radioprotectors was designed and synthesized. Three key elements in the aminothiol design were, (1) small size for efficient transmembrane diffusion, (2) positive charged amines in alkyl backbone for strong ionic interaction with DNA backbone, and (3) a perpendicular, alkyl side-chain with a terminal thiol that is projected away from the DNA backbone to enable reactive oxygen species scavenging around DNA. Several in vitro assays were used to characterize the prototype aminothiol, PrC-210, for efficacy: protection against reactive oxygen species-induced plasmid DNA nicking, mass spectrometry to detect aminothiol-reactive oxygen species by-products, S.

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The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol, and its polyamine and thiolated polyamine progenitors are reported. All of the molecules significantly inhibited growth of cultured normal human fibroblasts. The combination of an ROS-scavenging thiol group and a positively charged alkyl-amine backbone provided the most radioprotective aminothiol molecule.

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