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ANALYTICAL CURRENTS Combinatorial chemistry for biological targets Dario Neri and co-workers at ETH Zürich (Switzerland) have developed a new combinatorial chemistry strategy that uses an encoded self-assembling chemical (ESAC) library to screen for chemicals that bind to biological targets. Such a library could offer an alternative to antibodies and aptamers. The ESAC library consists of 137 chemical compounds bound to oligonucleotides (oligos). Other chemicals that are known to bind to the target are introduced on a complementary oligo. When complementary oligos hybridize, twocompound candidate binders are created. The target biological molecule is then introduced, and binders to that target are enriched. The binders are identified by
Redox control of EOF Charles Martin and Scott Miller of the University of Florida have found a new way to manipulate the electroosmotic flow (EOF) of solutions in small channels. The researchers coated the inside walls of carbon nanotubes with the redox-active polymer, poly(vinylferrocene). When they applied a low voltage for a few seconds, the polymer changed oxidation states and switched between electrically neutral and positively charged forms. By controlling the surface charge on the nanotube walls, the researchers controlled the rate and direction of EOF through membranes lined with the carbon nanotubes. The new approach should be applicable to any device that uses EOF, as long as the channels are electronically conductive and can be coated with the polymer. (J. Am. Chem. Soc. 2004, 126, 6226–6227) © 2004 AMERICAN CHEMICAL SOCIETY
performing PCR on the oligos, which carry short tag sequences. The PCR products can be sequenced or screened on a microarray. To test the method, the researchers added a biotinylated oligo to the ESAC library. A dummy oligo that was not attached to a candidate chemical, but was complementary to the library sequences, was also added. When streptavidin was introduced as the target molecule, biotin was specifically enriched 750-fold over other chemicals represented in the library. Neri and co-workers then used the ESAC library in combination with two known lead compounds to find chemicals that bind to human serum albumin (HSA) and bovine carbonic anhydrase II (CA). Although some compounds bound equally well to both HSA and CA, others bound
preferentially to only one of the targets. Positive combinations were synthesized as two-chemical ligands with linkers to study their binding properties. Synergistic effects were observed in which some libraryderived chemicals had a higher binding affinity when coupled to one of the known lead compounds than either chemical had on its own. (Nat. BiotechTarget nol. 2004, 22, 568–574) A schematic of an ESAC library member bound to a target. (Adapted with permission. Copyright 2004 Macmillan Publishing Ltd.)
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LC/ESI-MS chiral analysis Combining chiral LC separations with electrospray ionization (ESI) MS detection is not simple because LC mobile phases and additives are typically not compatible with MS instrumentation. Most researchers who couple chiral LC and MS perform postcolumn dilution with MS-compatible solvents, which compromises resolution and sensitivity. Common LC additives, such as phosphate buffers, can also adversely affect MS detection. To get around these problems, Daniel Armstrong and Meera Desai at Iowa State University tested various mobile phases, additives, and flow rates until they found the optimal conditions for the LC/ESI-MS chiral analysis of 19 pharmaceutical compounds. The researchers used macrocyclic glycopeptide-based stationary phases in both reversedphase and polar organic modes. Chromatographic resolution and selectivity were essentially unchanged when the researchers used MS-compatible additives in the mobile phases. The type of volatile additive, however, affected the signal intensity. Lower detection limits and better sensitivities were obtained with polar organic solvents than with reversed-phase solvents. The researchers say that the high amount of water in reversed-phase solvents may lower the efficiency of ESI. Low flow rates and narrow-bore columns greatly enhanced sensitivity and resolution. (J. Chromatogr. A 2004, 1035, 203–210)
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