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LC/MS evaluation of metabolism and membrane transport of bombesin peptides
Gu Dongyu; Ma Ying; Niu Gang; Yan Yongjun; Lang Lixin; Aisaand Haji Akber; Gao Haokao; Kiesewetter Dale O.; Chen Xiaoyuan
2011
Source PublicationAMINO ACIDS
ISSN0939-4451
Volume40Issue:2Pages:669-675
AbstractTwo bombsin peptides, GRPR agonist Aca-QWAVGHLM-NH(2) and antagonist fQWAVGHL-NHEthyl were evaluated. We employed the highly sensitive Waters Q-Tof Premier MS coupled with a UPLC system to identify the metabolites produced by rat hepatocytes or PC-3 human prostate cancer cells; and we utilized the AB/MDS 4000 Q-Trap LC/MS/MS system with highly sensitive quantitative and qualitative performance, to quantitatively analyze the internalization of GRPR agonist and antagonist in PC-3 cells. The major metabolites of both GRPR agonist and antagonist were the result of peptide bond hydrolysis between W and A which was demonstrated by observation of the N-terminal fragment m/z 446 (Aca-QW-OH) for agonist and m/z 480 (fQW-OH) for antagonist. Both peptides were also hydrolyzed between A and V which formed peaks m/z 517 Aca-QWA-OH and m/z 555 (VGHLM-NH2) for the agonist and m/z 551 fQWA-OH and m/z 452 (VGHL-NHEthyl) for the antagonist. The peptide agonist also formed a unique metabolite that resulted from hydrolysis of the C-terminal amide. The antagonist showed significantly slower metabolism as compared to the agonist in both rat hepatocytes and PC-3 cells. The antagonist also showed significantly lower PC-3 cell internalization rate than that of the agonist. In conclusion, the metabolism profiles of both GRPR agonist and antagonist peptides were identified by LC/MS. The antagonist peptide was more stable than the agonist peptide in rat hepatocyte incubation. One major factor could be the hydrolysis-resistant C-terminal L-NHEthyl group compared with the unsubstituted amide of the agonist. Another factor could be different amino acid sequences of the agonist and antagonist that may also influence the enzymatic hydrolysis. The antagonist ligand is potentially more useful for receptor-targeted imaging due primarily to its higher metabolic stability.
KeywordLc/ms/ms Gastrin-releasing Peptide Receptor (Grpr) Bombesin (Bbn) Agonist Antagonist
Subject AreaBiochemistry & Molecular Biology
DOI10.1007/s00726-010-0696-y
Indexed BySCI
WOS IDWOS:000286189600035
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/1673
Collection资源化学研究室
AffiliationNIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA;Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Urumqi, Peoples R China;Chinese Acad Sci, Grad Univ, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Gu Dongyu,Ma Ying,Niu Gang,et al. LC/MS evaluation of metabolism and membrane transport of bombesin peptides[J]. AMINO ACIDS,2011,40(2):669-675.
APA Gu Dongyu.,Ma Ying.,Niu Gang.,Yan Yongjun.,Lang Lixin.,...&Chen Xiaoyuan.(2011).LC/MS evaluation of metabolism and membrane transport of bombesin peptides.AMINO ACIDS,40(2),669-675.
MLA Gu Dongyu,et al."LC/MS evaluation of metabolism and membrane transport of bombesin peptides".AMINO ACIDS 40.2(2011):669-675.
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