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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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An adjustable release rate linking strategy for cytotoxin-peptide conjugates.

Peptide hormones are often rapidly internalized after binding to and activation of their receptors which are sometimes over-expressed on tumor cells. Thus, peptide ligands are increasingly being utilized for specific tumor cell targeting and internalization of radioactive isotopes for tumor imaging and for specifically delivering and internalizing cytotoxic moieties. Here, we describe a new carbamate linker system containing a series of built-in nucleophile assisted releasing (BINAR) groups which enable the 'fine-tuning' of intracellular cleavage rates of free cytotoxic agents containing reactive OH groups. Release rates were found to fit well with the chemical model and several conjugates of camptothecin and one of combretastatin were shown to have potent cytotoxic effects on cultures of human neuroblastoma IMR-32 cells which over-express somatostatin receptors.[1]

References

  1. An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Fuselier, J.A., Sun, L., Woltering, S.N., Murphy, W.A., Vasilevich, N., Coy, D.H. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
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