Cyclic and acyclic oxorhenium(V)-peptide conjugates as new ligands of the human cyclophilin hCyp-18.
Peptide metalloconstructs display interesting conformations, activities, and resistance to proteolysis. However, introduction of a metal core close to the residues that interact with the protein might strongly affect the binding. We investigated the effects of a coordinated oxorhenium core on the binding of model peptides to cyclophilin hCyp-18, a protein implicated in important biological processes and several diseases. For this purpose, we synthesized a series of linear metalloconstructs bearing an oxorhenium(V) core (ReO3+), as well as a peptide cyclized through oxorhenium(V) coordination. All these peptides contain an Ala-Pro-Xaa-pNA moiety (Xaa = Cys derivative) and are anticipated to bind simultaneously to the S1-S1' and S2'-S3' subsites of hCyp-18. Therefore, the metal core is coordinated to both the cysteine residue and exogenous or endogenous NS2 tridentate systems. Cyclization of the peptide through metal coordination did not affect the affinity whereas bimolecular oxorhenium metalloconstructs bind hCyp-18 with a slightly better affinity than the corresponding nonmetalated peptide. Peptide labeling with a 99mTcO3+ core was also carried out successfully.
Clavaud
Cécile
C
CEA/Saclay, Département d'Ingénierie et d'Etudes des Protéines, Bâtiment 152, 91191 Gif-sur-Yvette, France.
Heckenroth
Marion
M
Stricane
Charlotte
C
Ménez
André
A
Dugave
Christophe
C
D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D012211:Rhenium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D008024:Ligands; D010455:Peptides; C437224:cyclophilin hCyp-18; C015428:perrhenate; D012211:Rhenium; D021983:Cyclophilins