Document Detail

Evaluation of fluorine-labeled gastrin-releasing peptide receptor (GRPR) agonists and antagonists by LC/MS.
MedLine Citation:
PMID:  22354143     Owner:  NLM     Status:  MEDLINE    
An LC/MS method was used to evaluate 2-fluoropropionyl (FP) and 4-fluorobenzoyl (FB) modified bombsin peptides: GRPR agonist [Aca-QWAVGHLM-NH(2)] and antagonist [fQWAVGHL-NHEt], and their hydrophilic linker modified counterparts with the attachment of GGGRDN sequence. This study developed strategies to evaluate the in vitro receptor mediated cell uptake and metabolic profile of the various GRPR agonists and antagonists. We identified the metabolites produced by rat hepatocytes and quantitatively analyzed the uptake and internalization of the ligands in PC-3 human prostate cancer cells. The major metabolites of both GRPR agonists and antagonists were the result of peptide bond hydrolysis between WA and AV. The agonists also formed a unique metabolite resulting from hydrolysis of the C-terminal amide. The antagonists showed significantly higher stability against metabolism compared to the agonists in rat hepatocytes. The directly modified agonists (FP-BBN and FB-BBN) had higher internalization with similar cell binding compared to the unmodified agonist (BBN), whereas the hydrophilic linker modified agonists (G-BBN and FG-BBN) had much lower total cell uptake. The labeled antagonists (FP-NBBN, FB-NBBN, G-NBBN and FP-G-NBBN) displayed lower internalization. The optimal imaging agent will depend on the interplay of ligand metabolism, cellular uptake, and internalization in vivo.
Ying Ma; Min Yang; Haokao Gao; Gang Niu; Yongjun Yan; Lixin Lang; Dale O Kiesewetter; Xiaoyuan Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2012-02-22
Journal Detail:
Title:  Amino acids     Volume:  43     ISSN:  1438-2199     ISO Abbreviation:  Amino Acids     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-21     Completed Date:  2013-01-31     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  9200312     Medline TA:  Amino Acids     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  1625-32     Citation Subset:  IM    
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Dr, Suite 1C14, Bethesda, MD 20892-2281, USA.
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MeSH Terms
Amino Acid Sequence
Biological Transport
Bombesin / analogs & derivatives*,  metabolism*,  pharmacology
Cell Line, Tumor
Chromatography, Liquid
Fluorine Radioisotopes
Hepatocytes / drug effects,  metabolism
Hydrophobic and Hydrophilic Interactions
Molecular Sequence Data
Neurotransmitter Agents / chemistry,  metabolism*,  pharmacology
Oligopeptides / analysis*
Rats, Sprague-Dawley
Receptors, Bombesin / agonists*,  antagonists & inhibitors*,  metabolism
Tandem Mass Spectrometry
Grant Support
Reg. No./Substance:
0/Fluorine Radioisotopes; 0/Neurotransmitter Agents; 0/Oligopeptides; 0/Receptors, Bombesin; 31362-50-2/Bombesin

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