The beta-glucuronyl-based prodrug strategy allows for its application on beta-glucuronyl-platinum conjugates.
The use of platinum drugs in antitumour therapy is well established. An important drawback of these chemotherapeutics is the lack of selectivity for tumour cells, usually resulting in severe toxic side effects. A glucuronyl-platinum conjugate was designed and synthesised to test the compatibility of platinum compounds with beta-glucuronidase-based prodrug therapy. Instantaneous cleavage of the beta-glucuronic bond in the glucuronyl-platinum conjugate was observed upon addition of beta-glucuronidase resulting in Pt(II)(dach)(4-hydroxybenzylmalonate) and glucuronic acid.
Tromp
Reynier A
RA
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
van Boom
Stella S G E
SS
Marco Timmers
C
C
van Zutphen
Steven
S
van der Marel
Gijsbert A
GA
Overkleeft
Herman S
HS
van Boom
Jacques H
JH
Reedijk
Jan
J
D005966:Glucuronidase / Q000737:chemistry*; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D017671:Platinum Compounds / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*
D017671:Platinum Compounds; D011355:Prodrugs; D005966:Glucuronidase