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Potential of collagen-like triple helical peptides as drug carriers: Their in vivo distribution, metabolism, and excretion profiles in rodents

Authors

  • Hiroyuki Yasui,

    1. Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
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  • Chisato M. Yamazaki,

    1. Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan
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  • Hiroshi Nose,

    1. Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan
    2. R and D Center, Kola-Gen Pharma Incorporation, Tokyo, Japan
    3. Institute of Chemical Biology, Waseda University, Tokyo, Japan
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  • Chihiro Awada,

    1. Laboratory of Protein Profiling and Functional Proteomics, Institute for Protein Research, Osaka University, Osaka, Japan
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  • Toshifumi Takao,

    1. Laboratory of Protein Profiling and Functional Proteomics, Institute for Protein Research, Osaka University, Osaka, Japan
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  • Takaki Koide

    Corresponding author
    1. Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan
    2. Institute of Chemical Biology, Waseda University, Tokyo, Japan
    3. Laboratory of Visiting Scientist, Institute for Protein Research, Osaka University, Osaka, Japan
    • Correspondence to: Takaki Koide, Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan; e-mail: koi@waseda.jp

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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

ABSTRACT

Collagen-model peptides composed of (X-Y-Gly)n sequences were used to study the triple helical structure of collagen. We report the stability of these collagen-like peptides in biological fluids, and their pharmacokinetics including distribution, metabolism, and excretion in animals. A typical collagen-model peptide, H-(Pro-Hyp-Gly)10-OH, was found to be extremely stable in the plasma and distributed mainly in the vascular blood space, and was eliminated through glomerular filtration in the kidneys. Triple helical peptides of (X-Y-Gly)n sequences were quantitatively recovered from the urine of rats after intravenous injection regardless of the differences in peptide net charge between −3 and +6 per triple helix. In contrast, the renal clearance became less efficient when the number of triplet repeats (n) was 12 or more. We also demonstrated the application of a collagen-like triple helical peptide as a novel drug carrier in the blood with a high urinary excretion profile. We further demonstrated that a collagen-like triple helical peptide conjugated to a spin probe, PROXYL, has the potential to evaluate the redox status of oxidative stress-induced animals in vivo. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 705–713, 2013.

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