Asteropsins B-D, sponge-derived knottins with potential utility as a novel scaffold for oral peptide drugs

作者：Li Huayue; Bowling John J; Su Mingzhi; Hong Jongki; Lee Bong Jin; Hamann Mark T^*; Jung Jee H

来源：Biochimica et Biophysica Acta-General Subjects, 2014, 1840(3): 977-984.

DOI：10.1016/j.bbagen.2013.11.001

• Knottin
• Marine sponge
• Asteropus sp.
• NMR
• Solution structure
• Oral peptide drug delivery

Background: Known linear knottins are unsuitable as scaffolds for oral peptide drug due to their gastrointestinal instability. Herein, a new subclass of knottin peptides from Porifera is structurally described and characterized regarding their potential for oral peptide drug development. %26lt;br%26gt;Methods: Asteropsins B-D (ASPB, ASPC, and ASPD) were isolated from the marine sponge Asteropus sp. The tertiary structures of ASPB and ASPC were determined by solution NMR spectroscopy and that of ASPD by homology modeling. %26lt;br%26gt;Results: The isolated asteropsins B-D, together with the previously reported asteropsin A (ASPA), compose a new subclass of knottins that share a highly conserved structural framework and remarkable stability against the enzymes in gastrointestinal tract (chymotrypsin, elastase, pepsin, and trypsin) and human plasma. %26lt;br%26gt;Conclusion: Asteropsins can be considered as promising peptide scaffolds for oral bioavailability. %26lt;br%26gt;General significance: The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides.

• 出版日期2014-3