Synthesis of oligotuftsin-based branched oligopeptide conjugates for chemotactic drug targeting. |
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Authors: | Gbor Mez Orsolya Lng Annamria Jakab Katalin B Bai Ildik Szab Gitta Schlosser Julianna Lng Lszl Khidai Ferenc Hudecz |
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Institution: | Research Group of Peptide Chemistry, Hungarian Academy of Sciences, E?tv?s L. University, 1518 Budapest, Hungary. hogyishivjak@yahoo.com |
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Abstract: | The synthesis and chemotactic properties of a new class of branched oligopeptide-based conjugates are described. Tetratuftsin derivatives containing chemotactic formyl tripeptides (For-MLF, For-NleLF or For-MMM) in branches were prepared by stepwise solid-phase peptide synthesis. The influence of the composition and ionic charge of the carrier-branched oligopeptide on the chemotactic behaviour of the conjugate was studied in Tetrahymena pyriformis. Conjugates with methotrexate (Mtx) as a drug component was also prepared. For this, a GFLGC spacer, cleavable by cathepsin B, was used. The spacer with N-terminal methotrexate was coupled to the chloroacetylated chemotactic carrier molecule by thioether bond formation. The chemotactic activity and cytotoxity of Mtx conjugates were also studied. |
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Keywords: | drug targeting chemotactic peptide tetratuftsin methotrexate conjugation thioether linkage chemotaxis cytotoxicity |
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