| <i>In Vivo</i> Biodistribution and Small Animal PET of <sup>64</sup>Cu Labeled Antimicrobial Peptoids. | |
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MedLine Citation:
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PMID: 22486390 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Peptoids are a rapidly developing class of biomimetic polymers based on oligo-<i>N</i>-substituted glycine backbones, designed to mimic peptides and proteins. Inspired by natural antimicrobial peptides, a group of cationic amphipathic peptoids has been successfully discovered with a potent and broad-spectrum activity against pathogenic bacteria; however, there are limited studies to address the <i>in vivo</i> pharmacokinetics of the peptoids. Herein, <sup>64</sup>Cu labeled DOTA conjugates of three different peptoids and two control peptides were synthesized and assayed <i>in vivo</i> by both biodistribution studies and small animal positron emission tomography (PET). The study was designed in a way to assess how structural differences of the peptidomimetics affect <i>in vivo</i> pharmacokinetics. As amphipathic molecules, major uptake of the peptoids occurred at the liver. Increased kidney uptake was observed by deleting one hydrophobic residue in the peptoid, and <sup>64</sup>Cu-3 achieved the highest kidney uptake of all the conjugates tested in this study. In comparison to peptides, our data indicated that peptoids had general <i>in vivo</i> properties of higher tissue accumulation, slower elimination, and higher <i>in vivo</i> stability. Different administration routes (intravenous, intraperitoneal, and oral) were investigated with peptoids. When administered orally, the peptoids showed poor bioavailability, reminiscent to that of peptide. But, remarkably longer passage through the gastrointestinal (GI) tract without rapid digestion was observed for peptoids. These unique <i>in vivo</i> properties of peptoids were rationalized by efficient cellular membrane permeability and protease resistance of peptoids. The results observed in the biodistribution studies could be confirmed by the PET imaging, which provides a reliable way to evaluate <i>in vivo</i> pharmacokinetic properties of peptoids noninvasively and in real time. The pharmacokinetic data presented here can provide an insight for further development of the antimicrobial peptoids as pharmaceuticals. |
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Authors:
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Zhen Cheng; Annelise E Barron; Jiwon Seo; Gang Ren; Hongguang Liu; Zheng Miao; Minyoung Park; Tyler M Miller |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-9 |
Journal Detail:
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Title: Bioconjugate chemistry Volume: - ISSN: 1520-4812 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9010319 Medline TA: Bioconjug Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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