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


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


CONCLUSIONS
The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides.
College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: lihuayue@naver.com.
Huayue
H
Li
Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, Oxford, MN 38677, USA. Electronic address: bowlingjj@gmail.com.
John J
JJ
Bowling
College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: smz0310@163.com.
Mingzhi
M
Su
College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: jhong@khu.ac.kr.
Jongki
J
Hong
College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: lbj@nmr.snu.ac.kr.
Bong-Jin
BJ
Lee
Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, Oxford, MN 38677, USA. Electronic address: mthamann@olemiss.edu.
Mark T
MT
Hamann
College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: jhjung@pusan.ac.kr.
Jee H
JH
Jung
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D057771:Cystine-Knot Miniproteins / Q000737:chemistry*; D055808:Drug Discovery; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011161:Porifera / Q000737:chemistry*; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D057771:Cystine-Knot Miniproteins; D002118:Calcium
Asteropus sp.; Knottin; Marine sponge; NMR; Oral peptide drug delivery; Solution structure