Binding compounds selectivity

Violette SM, Shakespeare WC, Bartlett C, Guan W, Smith JA, Rickies RJ, Bohacek RS, Holt DA, Baron R, Sawyer TK. A Src SH2 selective binding compound inhibits osteoclast-mediated resorption. Chem Biol 2000 7 225-235. 

A similar strategy was employed to identify a DPP-IV inhibitor (6) with good in vivo potency in a mouse model of diabetes [44], Plasma protein binding, as assessed by shift assay (50% serum), was presented for all final compounds. The compound selected as having the best overall profile was active in vivo at 0.1 mg/kg. The activity at 1 h post-dose was consistent with the free drug principle - total plasma concentration 269 nM murine-free fraction 4% unbound plasma concentration 11 nM in vitro potency versus murine DPP-IV 6nM. 

Klekota, B. Hammond, M. H. Miller, B. L. Generation of novel DNA-binding compounds by selection and amplification from self-assembled combinatorial libraries. Tetrahedron Lett. 1997, 38, 8639-8643. 

Klekota, B. Miller, B. L. Selection of DNA-binding compounds via multistage molecular evolution. Tetrahedron 1999, 55, 11687 (Combinatorial Chemistry Symposium in Print). 

Carbohydrates and glycosides recently emerged as a novel class of nucleic acid binding compounds. A detailed study of the factors affecting the site-selectivity of some recently discovered antitumor antibiotics has shed new light on the role that oligosaccharides may play in nucleic acid recognition. 

The antibiotics are compounds secreted by microbes that enhance the permeability of membranes to cations. One class functions by binding a metal to give a liposoluble complex that can then pass across the membrane. Examples are valinomycin, a cyclic peptide that binds K+ selectively, and monensin which binds Na+. These too are oxygen-donor ligands, and will be discussed in the following section. They function as antibiotics because they allow the concentrations of a cation across membranes to become equalized, and so cause the collapse of the membrane potential. 

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