title: Identification of antihyperuricemic peptides in the proteolytic digest of shark cartilage water extract using in vivo activity-guided fractionation.
abstract: A peptide that exerts antihyperuricemic activity after oral administration was identified from a microbial protease (alcalase) digest of the water extract of shark cartilage by in vivo activity-guided fractionation, using oxonate-induced hyperuricemic rats. Water extract of shark cartilage was first fractionated by preparative ampholine-free isoelectric focusing, followed by preparative reversed-phase liquid chromatography. The antihyperuricemic activity of the alcalse digests of the obtained fractions was evaluated using an animal model. Alcalase digests of the basic and hydrophobic fractions exerted antihyperuricemic activity. A total of 18 peptides were identified in the alcalase digest of the final active fraction. These peptides were chemically synthesized and evaluated for antihyperuricemic activity. Tyr-Leu-Asp-Asn-Tyr and Ser-Pro-Pro-Tyr-Trp-Pro-Tyr lowered the serum uric acid level via intravenous injection at 5 mg/kg of body weight. Furthermore, orally administered Tyr-Leu-Asp-Asn-Tyr showed antihyperuricemic activity. Therefore, these peptides are at least partially responsible for the antihyperuricemic activity of the alcalase digest of shark cartilage.
authors.affiliation: Central Research Institute, Maruha Nichiro Holdings, Incorporated 16-2 Wadai, Tsukuba, Ibaraki 300-4295, Japan.
authors.forename: Itsuki
authors.initials: I
authors.lastname: Murota
authors.forename: Satoko
authors.initials: S
authors.lastname: Taguchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Sato
mesh_terms: D000595:Amino Acid Sequence; D058500:Animal Fins / Q000737:chemistry*; D000818:Animals; D004063:Digestion; D006074:Gout Suppressants / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D012754:Sharks; D014020:Tissue Extracts / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D014527:Uric Acid / Q000097:blood
chemical_list: D006074:Gout Suppressants; D010455:Peptides; D014020:Tissue Extracts; C111481:shark cartilage extract; D014527:Uric Acid