(WFRF:(Ross D.)) srt2:(2005-2009)
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Structural Properties of Relaxin Chimeras: NMR Characterization of the R3/I5 Relaxin Peptide
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- Haugaard-Kedström (published under the name Haugaard-Jönsson), Linda M. (author)
- Högskolan i Kalmar,Naturvetenskapliga institutionen
- Hossain, M. Akhter (author)
- Daly, Norelle L. (author)
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- Bathgate, Ross A.D. (author)
- Wade, John D. (author)
- Craik, David J. (author)
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- (creator_code:org_t)
- 2009-04-10
- 2009
- English.
- In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1160, s. 27-30
- Journal article (peer-reviewed)
Abstract
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- Relaxin-3 interacts with high potency with three relaxin family peptide receptors (RXFP1, RXFP3, and RXFP4). Therefore, the development of selective agonist and antagonist analogs is important for in vivo studies characterizing the biological significance of the different receptor-ligand systems and for future pharmaceutical applications. Recent reports demonstrated that a peptide selective for RXFP3 and RXFP4 over RXFP1 can be generated by the combination of the relaxin-3 B chain with the A chain from insulin-like peptide 5 (INSL5), creating an R3/I5 chimera. We have used NMR spectroscopy to determine the three-dimensional structure of this peptide to gain structural insights into the consequences of combining chains from two different relaxins. The R3/I5 structure reveals a similar backbone conformation for the relaxin-3 B chain compared to native relaxin-3, and the INSL5 A chain displays a relaxin/insulin-like fold with two parallel helices. The findings indicate that binding and activation of RXFP3 and RXFP4 mainly require the B chain and that the A chain functions as structural support. RXFP1, however, demonstrates a more complex binding mechanism, involving both the A chain and the B chain. The creation of chimeras is a promising strategy for generating new structure-activity data on relaxins.
Subject headings
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Keyword
- Organic Chemistry
- Organisk kemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Linnaeus University
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