4.5 Article

Lectin-directed enzyme activated prodrug therapy (LEAPT): Synthesis and evaluation of rhamnose-capped prodrugs

期刊

JOURNAL OF DRUG TARGETING
卷 18, 期 10, 页码 794-802

出版社

INFORMA HEALTHCARE
DOI: 10.3109/1061186X.2010.529909

关键词

Lectins; carbohydrates; doxorubicin; 5-fluorouracil; prodrug; enzyme release; l-rhamnose; d-galactose

资金

  1. Glycoform Ltd.
  2. Biotechnology and Biological Sciences Research Council [BB/C510824/1, BB/E004350/1, EGA17763] Funding Source: researchfish
  3. Engineering and Physical Sciences Research Council [EP/D023335/1, GR/T26542/01, EP/G026688/1, EP/D023343/1, EP/E000614/1] Funding Source: researchfish
  4. BBSRC [BB/E004350/1] Funding Source: UKRI
  5. EPSRC [EP/E000614/1, EP/G026688/1] Funding Source: UKRI

向作者/读者索取更多资源

The lectin-directed enzyme activated prodrug therapy (LEAPT) bipartite drug delivery system utilizes glycosylated enzyme, localized according to its sugar pattern, and capped prodrugs released by that enzyme. In this way, the sugar coat of a synthetic enzyme determines the site of release of a given drug. Here, prodrugs of doxorubicin and 5-fluorouracil capped by the nonmammalian L-rhamnosyl sugar unit have been efficiently synthesized and evaluated for use in the LEAPT system. Both are stable in blood, released by synthetically D-galactosylated rhamnosidase enzyme, and do not inhibit the uptake of the synthetic enzyme to its liver target. These results are consistent with their proposed mode of action and efficacy in models of liver cancer, and confirm modular flexibility in the drugs that may be used in LEAPT.

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