Title
Stable and biocompatible cystine knot peptides from the marine sponge Asteropus sp.
Author
Mingzhi Su, Huayue Li, Haibo Wang, Eun La Kim, Hyung Sik Kim, Eun-Hee Kim, Jaewon Lee, Jee H. Jung
Year
2016
Journal
Bioorganic and Medicinal Chemistry
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.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Protein denaturation, Thermal stability, Pharmaceutical, Biochemistry