TY - JOUR
T1 - Fe in biosynthesis, translocation, and signal transduction of NO
T2 - Toward bioinorganic engineering of dinitrosyl iron complexes into NO-delivery scaffolds for tissue engineering
AU - Hsiao, Hui Yi
AU - Chung, Chieh Wei
AU - Santos, Joshua H.
AU - Villaflores, Oliver B.
AU - Lu, Tsai Te
N1 - Publisher Copyright:
© 2019 The Royal Society of Chemistry.
PY - 2019
Y1 - 2019
N2 - Iron, the most abundant transition metal ion in humans, participates in the biosynthesis, translocation, signal transduction, and transformation of nitric oxide through its encapsulation in the form of heme, [Fe-S], and [Fe(NO)2] cofactors within a variety of enzymes and proteins. After the review on nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) for the biosynthesis and detection of NO, in this report, we discuss the natural utilization of the [Fe(NO)2] motif for translocation of endogenous NO and the translational development of synthetic dinitrosyl iron complexes (DNICs) for biomedical applications. A mechanistic study of NO-release and NO-transfer reactivity of structure-characterized DNICs promoted the discovery of cell-penetrating and in vivo NO-delivery reactivity for treatment of cancer and wound healing in diabetes. Beyond activation of sGC and vasodilation, phase I/II clinical trials of glutathione-bound DNICs (Oxacom®) against hypertension encourage bioinorganic engineering of DNICs into scaffolds for tissue regeneration and repair relying on anti-bacterial, anti-inflammation, cytoprotective, and proliferative effects of NO.
AB - Iron, the most abundant transition metal ion in humans, participates in the biosynthesis, translocation, signal transduction, and transformation of nitric oxide through its encapsulation in the form of heme, [Fe-S], and [Fe(NO)2] cofactors within a variety of enzymes and proteins. After the review on nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) for the biosynthesis and detection of NO, in this report, we discuss the natural utilization of the [Fe(NO)2] motif for translocation of endogenous NO and the translational development of synthetic dinitrosyl iron complexes (DNICs) for biomedical applications. A mechanistic study of NO-release and NO-transfer reactivity of structure-characterized DNICs promoted the discovery of cell-penetrating and in vivo NO-delivery reactivity for treatment of cancer and wound healing in diabetes. Beyond activation of sGC and vasodilation, phase I/II clinical trials of glutathione-bound DNICs (Oxacom®) against hypertension encourage bioinorganic engineering of DNICs into scaffolds for tissue regeneration and repair relying on anti-bacterial, anti-inflammation, cytoprotective, and proliferative effects of NO.
UR - http://www.scopus.com/inward/record.url?scp=85068433559&partnerID=8YFLogxK
U2 - 10.1039/c9dt00777f
DO - 10.1039/c9dt00777f
M3 - 文献综述
C2 - 30990502
AN - SCOPUS:85068433559
SN - 1477-9226
VL - 48
SP - 9431
EP - 9453
JO - Dalton Transactions
JF - Dalton Transactions
IS - 26
ER -
