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1). In a proof-of-concept study, anticancer drug methotrexate (MTX) was used as a model drug. Two proteins known to interact with MTX, dihydrofolate reductase (DHFR) and deoxycytidine kinase (dCK), were identified by this approach as intracellular drug targets. This strategy based on multifunctionalized soluble nanopolymers demonstrates their potential to successfully probe drug-target proteins in vitro and in living cells. It has a number of advantages over existing methods including the presence of multiple sites of attachment to facilitate the synthesis of intracellular probes and, in combination with mass spectrometry, the ability to provide sensitive, fast identification of proteins of interest in the most physiologically relevant 3-deazaneplanocin A supplier environments. More importantly, a lot of hydrophobic or negatively charged drugs or prodrugs can be immobilized on dendrimers to improve their bioavailability. If at the same time they retain their bioactivity, it will broaden the application of this new strategy to many important biological systems. The procedure for immobilization of a compound on a solid support often involves a spacer arm to improve the efficiency of the interaction with target proteins in a cell lysate or tissue extract. Compounds are typically attached to the support through a long, hydrophilic linker such as a polyethylene glycol (PEG) chain31. Biological Erastin price activity of the linker-functionalized compound is then determined to confirm that it interacts with Ro3280 the same proteins as the parent molecule. Besides minimizing non-specific binding, the hydrophilic nature of the linker separates the probe compound from the surface of the resin and gives it greater conformational flexibility so that it can assume a favorable binding orientation and allow efficient target protein interaction. Sato et al.32 designed a rod-like polyproline helix linker instead of the more commonly used PEG group (Fig. 2). The chain of nine l-prolines formed a stable left-handed helix of length 27?? as measured by fluorescence resonance energy transfer experiments. The rigidity of the polyproline helix probably prevents its folding to permit better interaction with target proteins. In comparing the polyproline linker with a PEG linker of length 32??, Sato et al. found they could purify