title: Porphyrin-substituted H-NOX proteins as high-relaxivity MRI contrast agents.
abstract: Heme proteins are exquisitely tuned to carry out diverse biological functions while employing identical heme cofactors. Although heme protein properties are often altered through modification of the protein scaffold, protein function can be greatly expanded and diversified through replacement of the native heme with an unnatural porphyrin of interest. Thus, porphyrin substitution in proteins affords new opportunities to rationally tailor heme protein chemical properties for new biological applications. Here, a highly thermally stable Heme Nitric oxide/OXygen binding (H-NOX) protein is evaluated as a magnetic resonance imaging (MRI) contrast agent. T1 and T2 relaxivities measured for the H-NOX protein containing its native heme are compared to the protein substituted with unnatural manganese(II/III) and gadolinium(III) porphyrins. H-NOX proteins are found to provide unique porphyrin coordination environments and have enhanced relaxivities compared to commercial small-molecule agents. Porphyrin substitution is a promising strategy to encapsulate MRI-active metals in heme protein scaffolds for future imaging applications.
authors: Department of Chemistry, California Institute for Quantitative Biosciences, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720-3220, United States.
authors: Michael B
authors: MB
authors: Winter
authors: Piper J
authors: PJ
authors: Klemm
authors: Christine M
authors: CM
authors: Phillips-Piro
authors: Kenneth N
authors: KN
authors: Raymond
authors: Michael A
authors: MA
authors: Marletta
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006420:Hemeproteins / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D009569:Nitric Oxide / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D006420:Hemeproteins; D011166:Porphyrins; D009569:Nitric Oxide; D010100:Oxygen
references: Biometals. 2008 Aug;21(4):469-90
references: 18344005
references: Biophys J. 1999 Oct;77(4):2153-74
references: 10512835
references: Nat Nanotechnol. 2010 Nov;5(11):815-21
references: 20972435
references: J Am Chem Soc. 2008 Jul 23;130(29):9260-7
references: 18576649
references: J Am Chem Soc. 2012 May 16;134(19):8046-9
references: 22545921
references: Eur J Inorg Chem. 2012 Apr;2012(12):2108-2114
references: 23539072
references: J Am Chem Soc. 2006 Aug 9;128(31):10022-3
references: 16881625
references: Arch Biochem Biophys. 1980 Jun;202(1):1-7
references: 7396528
references: Contrast Media Mol Imaging. 2012 Jan-Feb;7(1):95-9
references: 22344885
references: Environ Sci Technol. 2009 Apr 15;43(8):2884-90
references: 19475966
references: Inorg Chem. 1999 Mar 8;38(5):1002-1005
references: 11670874
references: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12854-9
references: 15326296
references: Radiology. 1991 Jan;178(1):73-8
references: 1898538
references: J Am Chem Soc. 2011 Mar 2;133(8):2390-3
references: 21294571
references: J Inorg Biochem. 2011 Jun;105(6):784-92
references: 21497576
references: Nat Methods. 2007 Jan;4(1):43-5
references: 17187078
references: Nano Lett. 2009 Dec;9(12):4520-6
references: 19888720
references: J Am Chem Soc. 2011 Feb 2;133(4):649-51
references: 21171606
references: Chem Rev. 2008 Jun;108(6):2064-110
references: 18543879
references: Biochim Biophys Acta. 1959 Oct;35:543
references: 13837237
references: Acc Chem Res. 2009 Jul 21;42(7):893-903
references: 19537782
references: J Am Chem Soc. 2010 Apr 28;132(16):5582-3
references: 20373741
references: Bioorg Med Chem. 2010 Aug 15;18(16):5925-31
references: 20663676
references: Chem Commun (Camb). 2012 Feb 28;48(18):2436-8
references: 22273600
references: J Mol Biol. 2012 Sep 14;422(2):245-62
references: 22659321
references: J Inorg Biochem. 1990 Jan;38(1):17-25
references: 2159053