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

Psychiatry

Journal of Addiction Research & Therapy

Author(s): Li H, Bowling JJ, Su M, Hong J, Lee BJ,

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Abstract 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. Copyright © 2013 Elsevier B.V. All rights reserved.
This article was published in Biochim Biophys Acta and referenced in Journal of Addiction Research & Therapy

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