Re(I) and Tc(I) Complexes for Targeting Nitric Oxide Synthase: Influence of the Chelator in the Affinity for the Enzyme

Oliveira, Bruno L; Morais, Maurício; Mendes, Filipa; Moreira, Irina S; Cordeiro, Carlos; Fernandes, Pedro A; Ramos, Maria J; Alberto, Roger; Santos, Isabel; Correia, João D G

doi:10.1111/cbdd.12575

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Oliveira, B. L., Morais, M., Mendes, F., Moreira, I. S., Cordeiro, C., Fernandes, P. A., Ramos, M. J., Alberto, R., Santos, I., & Correia, J. D. G. (2015). Re(I) and Tc(I) Complexes for Targeting Nitric Oxide Synthase: Influence of the Chelator in the Affinity for the Enzyme. Chemical Biology & Drug Design, 86(5), 1072–1086. https://doi.org/10.1111/cbdd.12575

Abstract

Aiming to design 99mTc complexes for probing nitric oxide synthase (NOS) by SPECT, we synthesized conjugates (L4–L6) comprising a NOS-recognizing moiety connected to a diamino-propionic acid (dap) chelating unit. The conjugates led to complexes of the type fac-[M(CO)3(ĸ3-L)] (M = Re/99mTc; Re4/Tc4: L = L4; Re5/Tc5: L = L5; Re6/Tc6: L = L6). Enzymatic studies showed that L4 and L5, but not L6, gave complexes (Re4 and Re5) that are less potent than the conjugates. To rationalize these results, we performed docking and molecular dynamics