title: Stable and biocompatible cystine knot peptides from the marine sponge Asteropus sp.
abstract: Two new cystine knot peptides, asteropsins F (ASPF) and G (ASPG), were isolated from the marine sponge Asteropus sp. ASPF and ASPG are composed of 33 and 32 amino acids, respectively, and contain six cysteines which are involved in three disulfide bonds. They shared the characteristic features of the asteropsin family, such as, N-terminal pyroglutamate modification, incorporation of cis prolines, and the unique anionic profile, which distinguish them from other knottin families. Tertiary structures of the peptides were determined by high resolution NMR. ASPF and ASPG were found to be remarkably resistant not only to digestive enzymes (chymotrypsin, pepsin, elastase, and trypsin) but also to thermal degradation. In addition, these peptides were pharmacologically inert; non-hemolytic to human and fish red blood cells, non-stimulatory to murine macrophage cells, and nontoxic in vitro or in vivo. These observations support their stability and biocompatibility as suitable carrier scaffolds for the design of oral peptide drug.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Su
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Huayue
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Eun La
authors.initials: E
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang 363-883, Republic of Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: jhjung@pusan.ac.kr.
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D057771:Cystine-Knot Miniproteins / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D005399:Fishes; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D011161:Porifera / Q000737:chemistry*; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013696:Temperature
chemical_list: D001672:Biocompatible Materials; D057771:Cystine-Knot Miniproteins; D010455:Peptides; C000624171:asteropsin F; C000624172:asteropsin G
keywords: Anionic knottin; Asteropus sp.; Marine sponge; Oral peptide scaffold; Solution structure