In:
Dalton Transactions, Royal Society of Chemistry (RSC), Vol. 41, No. 10 ( 2012), p. 3001-3005
Abstract:
Platinum-based drugs play a crucial role in the fight against cancer. Oxaliplatin, which is used in the treatment of colorectal carcinoma, was the last platinum-based agent to be approved worldwide. However, the efficiency of the therapy is limited for example by a low accumulation of the drug in cancer cells. Cell-penetrating peptides (CPPs) are known to ease the cellular membranetransport and are used as vectors for low-molecular-weight drugs and drug carriers; of them, TATpeptides are the best-studied group. In this work, a TAT-peptide fragment (YGRKKRRQRRR) was for the first time conjugated to a platinum(iv) analog of oxaliplatin as a vehicle for membrane penetration. Solid-phase peptide synthesis and subsequent coupling with the platinum complex afforded mono- and difunctionalized conjugates, which were separated by preparative HPLC and characterized by analytical HPLC, ESI-MS, and 1H NMR spectroscopy. Both conjugates are active in the low micromolar range in CH1 and SW480 human cancer cells, requiring much lower concentrations than the untargeted analogs for equal effects.
Type of Medium:
Online Resource
ISSN:
1477-9226
,
1477-9234
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2012
detail.hit.zdb_id:
1472887-4
Bookmarklink