In:
European Journal of Inorganic Chemistry, Wiley, Vol. 2012, No. 17 ( 2012-06), p. 2877-2888
Abstract:
The reaction of the C ‐functionalized cyclam chelating agent 1,4,8,11‐tetraazacyclotetradecane‐6‐carboxylic acid ( 1 ) with CuCl 2 generated a stable and neutral complex 2 , which was characterized by elemental analysis, UV/Vis and IR spectroscopy, electrospray ionization mass spectrometry (ESI‐MS), EPR spectroscopy and X‐ray crystallography. The secondary amine groups of 1 were protected to generate 3 , which was further conjugated with the bombesin (BN) derivative H 2 N‐(Ornithine) 3 ‐BN(2–14) by a solid phase peptide synthesis method. After cleavage from the resin and deprotection, the resulting product 5 was obtained and characterized with ESI‐MS and NMR spectroscopy, and was subsequently complexed under mild conditions with CuCl 2 to generate complex 6 in high yield. Complex 6 was characterized with UV/Vis spectroscopy, ESI‐MS and EPR spectroscopy. The stability of complexes 2 and 6 was tested against cysteine, histidine and glutathione, and both complexes were found to be stable. The cyclam BN conjugate 5 and its Cu II complex 6 were suitable for targeting the gastrin releasing peptide receptors (GRPrs) that are over expressed on PC‐3 cells. Both 5 and 6 showed high binding affinity to GRPrs during in vitro cell assays with human PC‐3 prostate cancer cells. The half maximal inhibitory concentration ( IC 50 ) values observed for 5 and 6 (0.30 ± 0.03 and 0.33 ± 0.03 n M , respectively) were similar to that of the [Tyr] 4 ‐BN peptide (0.45 ± 0.04 n M ), which was used as standard.
Type of Medium:
Online Resource
ISSN:
1434-1948
,
1099-0682
DOI:
10.1002/ejic.v2012.17
DOI:
10.1002/ejic.201200049
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
1475009-0
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