Meeting News: New tricks from an old sol - Analytical Chemistry (ACS

Mar 1, 2001 - Meeting News: New tricks from an old sol. 2000 International Chemical Conference of Pacific Basin Societies—Elizabeth Zubritsky report...
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ANALYTICAL CURRENTS Ligands for SNPs Certain proteins in the DNA mismatch ty. Ligand binding is indicated by an cludes an aminoalkyl linker that can repair system, such as MutS, are famous increase of ~16 °C in the thermal stabbe used to immobilize the ligand on a for their ability to recognize mismatchility of the duplex. The second ligand— surface plasmon resonance (SPR) chip. es. The question has been whether rean extended version of the first—inSPR experiments were conducted using searchers can mimic this the ligand 2-immobilized ability and apply it to the chip and two versions of N DNA detection of single nucleoa 652-nucleotide-long seO N tide polymorphisms (SNPs). quence amplified from the Some researchers have tried N HSP70-2 gene. One version H 3C N N N to harness MutS and similar had a G–G mismatch at posiH N N natural proteins, but Kazuhiko tion 2345, and the other had O H H H Nakatani and colleagues at the normal G–C pair. SPR N H H Kyoto University (Japan) binding data confirmed N N H O R H have taken a different tack that the G–G duplex gave a by synthesizing two synthetic CH3 much stronger signal than N N N ligands that specifically recthe G–C pair, indicating seognize G–G mismatches. lective binding of the G–G O The first ligand employs mismatch. On the basis of 1 R=H dimeric naphthyridines. Naphthese results, the researchers 2 R = CH2CH2CH2NHCOCH2CH2CH2NH2 thyridine is a DNA intercalasuggest that such ligands tor that recognizes the bulge combined with SPR can be Structures of naphthyridine dimer ligands (green), versions 1 and 2, created by a mismatched G. used for high-throughput and the hydrogen bonding pattern to guanine (red). (Adapted with The dimer binds to G–G screening of SNPs. (Nat. Biotechnol. 2001, 19, 51–55) permission. Copyright 2001 Nature America.) mismatches with high affini-

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