Developing microcolin A analogs as biological probes |
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Authors: | Mandal Amit K Hines John Kuramochi Kouji Crews Craig M |
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Affiliation: | Department of Molecular, Cell, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA. |
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Abstract: | Three microcolin A and B analogs have been synthesized. Their biological activity profiles were evaluated against several cell lines, revealing the existence of a structural determinant whose role in mediating the antiproliferative effect of the microcolins has heretofore gone unrecognized. While previously described as potent immunosuppressive natural products, we found that these microcolin analogs possessed no selective cytotoxicity when comparing immune cell versus nonimmune cell proliferation. In addition, the amino-terminus of microcolin A has been modified to incorporate a biotinylated polyethylene glycol linker. The biological activity of this biotinylated microcolin A analog was determined. This affinity reagent was shown to retain limited biological activity and thus can serve as a useful probe for elucidating the mechanism of action of microcolin A. |
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