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学科主题: Biochemistry & Molecular Biology
题名: LC/MS evaluation of metabolism and membrane transport of bombesin peptides
作者: Gu Dongyu; Ma Ying; Niu Gang; Yan Yongjun; Lang Lixin; Aisaand Haji Akber; Gao Haokao; Kiesewetter Dale O.; Chen Xiaoyuan
关键词: LC/MS/MS ; Gastrin-releasing peptide receptor (GRPR) ; Bombesin (BBN) ; Agonist ; Antagonist
刊名: AMINO ACIDS
发表日期: 2011
DOI: 10.1007/s00726-010-0696-y
卷: 40, 期:2, 页:669-675
收录类别: SCI
资助者: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
摘要: Two 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.
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内容类型: 期刊论文
URI标识: http://ir.xjipc.cas.cn/handle/365002/1673
Appears in Collections:资源化学研究室_期刊论文

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作者单位: NIBIB, 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:
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.
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