Photolithographic Synthesis of Peptoids

摘要

Synthetic molecules capable of binding proteins with high specificity and affinity are potentially valuable reagents for chemical genetics studies, the construction of protein-detecting microarrays and a variety of other applications. Since protein-binding small molecules generally cannot be designed, they are almost always discovered by screening combinatorial libraries or compound collections. A significant development in this regard has been the development of small molecule microarrays. These are made by first creating a "one compound, one bead" library by split and pool techniques, sorting the beads into individual wells of microtiter plates, releasing the compounds from the beads, then using a robotic pin spotter to attach the compounds covalently to chemically modified glass slides in a defined array. The array can then be screened by incubation with a labeled protein under suitable conditions. This protocol has important advantages over screening bead-based libraries directly. Since very small amounts of compound are spotted onto a slide, it allows a library made on high-capacity beads to be replicated hundreds or thousands of times and also avoids a number of technical difficulties associated with screening on beads. However, spotted small-molecule microarrays are usually derived from encoded libraries of beads to allow the identification of each compound on the array. Many current encoding methods are expensive and require specialized equipment and infrastructure.