Stable and biocompatible cystine knot peptides from the marine sponge Asteropus sp

[Display omitted] 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 characteris...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2016-07, Vol.24 (13), p.2979-2987
Main Authors: Su, Mingzhi, Li, Huayue, Wang, Haibo, Kim, Eun La, Kim, Hyung Sik, Kim, Eun-Hee, Lee, Jaewon, Jung, Jee H.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Anionic knottin
Asteropus
Asteropus sp
Biocompatible Materials - chemistry
Biocompatible Materials - isolation & purification
Biocompatible Materials - pharmacology
Cell Line
Cystine-Knot Miniproteins - chemistry
Cystine-Knot Miniproteins - pharmacology
Erythrocytes - drug effects
Fishes
Humans
Macrophages - drug effects
Magnetic Resonance Spectroscopy
Marine
Marine sponge
Mice
Models, Molecular
Oral peptide scaffold
Peptides - chemistry
Peptides - genetics
Porifera - chemistry
Protein Stability
Protein Structure, Tertiary
Sequence Alignment
Solution structure
Temperature
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Summary:[Display omitted] 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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2016.05.006