Synthetic Covalently Linked Dimeric Form of H2 Relaxin Retains Native RXFP1 Activity and Has Improved In Vitro Serum Stability
Joint Authors
Separovic, Frances
Wade, John D.
Nair, Vinojini B.
Bathgate, Ross A. D.
Samuel, Chrishan S.
Hossain, Mohammed Akhter
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-01-22
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Human (H2) relaxin is a two-chain peptide member of the insulin superfamily and possesses potent pleiotropic roles including regulation of connective tissue remodeling and systemic and renal vasodilation.
These effects are mediated through interaction with its cognate G-protein-coupled receptor, RXFP1.
H2 relaxin recently passed Phase III clinical trials for the treatment of congestive heart failure.
However, its in vivo half-life is short due to its susceptibility to proteolytic degradation and renal clearance.
To increase its residence time, a covalent dimer of H2 relaxin was designed and assembled through solid phase synthesis of the two chains, including a judiciously monoalkyne sited B-chain, followed by their combination through regioselective disulfide bond formation.
Use of a bisazido PEG7 linker and “click” chemistry afforded a dimeric H2 relaxin with its active site structurally unhindered.
The resulting peptide possessed a similar secondary structure to the native monomeric H2 relaxin and bound to and activated RXFP1 equally well.
It had fewer propensities to activate RXFP2, the receptor for the related insulin-like peptide 3.
In human serum, the dimer had a modestly increased half-life compared to the monomeric H2 relaxin suggesting that additional oligomerization may be a viable strategy for producing longer acting variants of H2 relaxin.
American Psychological Association (APA)
Nair, Vinojini B.& Bathgate, Ross A. D.& Separovic, Frances& Samuel, Chrishan S.& Hossain, Mohammed Akhter& Wade, John D.. 2015. Synthetic Covalently Linked Dimeric Form of H2 Relaxin Retains Native RXFP1 Activity and Has Improved In Vitro Serum Stability. BioMed Research International،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1056550
Modern Language Association (MLA)
Nair, Vinojini B.…[et al.]. Synthetic Covalently Linked Dimeric Form of H2 Relaxin Retains Native RXFP1 Activity and Has Improved In Vitro Serum Stability. BioMed Research International No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1056550
American Medical Association (AMA)
Nair, Vinojini B.& Bathgate, Ross A. D.& Separovic, Frances& Samuel, Chrishan S.& Hossain, Mohammed Akhter& Wade, John D.. Synthetic Covalently Linked Dimeric Form of H2 Relaxin Retains Native RXFP1 Activity and Has Improved In Vitro Serum Stability. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1056550
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1056550