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

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• 作者：Huayue Li ; John J. Bowling ; Mingzhi Su ; Jongki Hong ; Bong-Jin Lee ; Mark T. Hamann ; Jee H. Jung
• 关键词：Knottin ; Marine sponge ; Asteropus sp. ; NMR ; Solution structure ; Oral peptide drug delivery
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：March, 2014
• 年：2014
• 卷：1840
• 期：3
• 页码：977-984
• 全文大小：1269 K

文摘

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.

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.

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.

Conclusion

Asteropsins can be considered as promising peptide scaffolds for oral bioavailability.

General significance

The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides.