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    
Abstract/OtherAbstract:
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.
Authors:
Ying Ma; Min Yang; Haokao Gao; Gang Niu; Yongjun Yan; Lixin Lang; Dale O Kiesewetter; Xiaoyuan Chen
Related Documents :
2450763 - Characterization of a substance p receptor activating a cation permeability in neuronal...
22292013 - Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.
2156193 - Veratrine supports the in vitro survival of embryonic chick sympathetic neurons.
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    
Affiliation:
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Biological Transport
Bombesin / analogs & derivatives*,  metabolism*,  pharmacology
Cell Line, Tumor
Chromatography, Liquid
Fluorine Radioisotopes
Hepatocytes / drug effects,  metabolism
Humans
Hydrolysis
Hydrophobic and Hydrophilic Interactions
Male
Molecular Sequence Data
Neurotransmitter Agents / chemistry,  metabolism*,  pharmacology
Oligopeptides / analysis*
Rats
Rats, Sprague-Dawley
Receptors, Bombesin / agonists*,  antagonists & inhibitors*,  metabolism
Tandem Mass Spectrometry
Grant Support
ID/Acronym/Agency:
Z99 EB999999/EB/NIBIB NIH HHS; ZIA EB000073-02/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Fluorine Radioisotopes; 0/Neurotransmitter Agents; 0/Oligopeptides; 0/Receptors, Bombesin; 31362-50-2/Bombesin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Predicting the lung compliance of mechanically ventilated patients via statistical modeling.
Next Document:  AW00179 potentiates TRAIL-mediated death of human lung cancer H1299 cells through ROS-JNK-c-Jun-medi...