title: Fecal Excretion of Orally Administered Collagen-Like Peptides in Rats: Contribution of the Triple-Helical Conformation to Their Stability.
abstract: Orally ingested peptides are generally digested in the gastrointestinal (GI) tract and absorbed in the form of oligopeptides. We previously reported that intravenously administered collagen-like triple-helical peptides circulated in the bloodstream and were excreted in their intact forms in urine nearly quantitatively. In the present study, we investigated the fates of orally administered collagen-like peptides in rats. (Pro-Hyp-Gly)10 (Hyp: 4-hydroxyproline), which formed a stable triple-helical structure, was stable in the GI tract, and 72.3±13.0% of the peptide was excreted in the feces. Its recovery ratio was similar to that of all-D-(Pro-Pro-Gly)10 (75.1±15.7%), the indigestible control. In contrast, (Pro-Hyp-Gly)5 and (Pro-Pro-Gly)10, the random coil conformations of which were dominant at body temperature, were not detected in fecal samples, indicating that they were digested by proteases. The high stability of the triple-helical conformation in mammalian bodies suggests the potential use of collagen-like peptides as novel scaffolds of peptide drugs.
authors.affiliation: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University.
authors.forename: Takaki
authors.initials: T
authors.lastname: Koide
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kazuma B
authors.initials: KB
authors.lastname: Taira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000737:chemistry*; D005243:Feces / Q000737:chemistry; D008297:Male; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010455:Peptides; D003094:Collagen