Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1–BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases

Lanthanide complexes of Tris-3,4-HOPO as potential imaging probes: complex stability, magnetic and Vis/NIR luminescence properties"

There is a growing interest on the development of new medical diagnostic tools with higher sensibility and less damage for the patient body, namely on imaging reporters for the management of diseases and optimization of treatment strategies. This article examines the properties of a new class of lanthanide complexes with a tripodal tris-3-hydroxy-4-pyridinone (Tris-3,4-HOPO) ligand - NTP(PrHP)3. Among the studies herein performed, a major relevance is given to the thermodynamic stability of the complexes with a series of Ln3+ ions (Ln = La, Pr, Gd, Er, Lu) and to the magnetic relaxation properties of the Gd3+ complex. This hexadentate ligand enables the formation of 1:1 Ln3+ complexes with high thermodynamic stability following the usual trend, while the Gd-chelates show improved relaxivity (higher hydration number), as compared with commercially available Gd-based contrast agents (CAs); transmetallation of the Gd3+-L complex with Zn2+ proved to be thermodynamically and kinetically disfavored. Therefore, NTP(PrHP)3 emerges as part of a recently proposed new generation of CAs with prospective imaging sensitivity gains

New tris-3,4-HOPO lanthanide complexes as potential imaging probes: complex stability and magnetic properties

There is a growing interest in the development of new medical diagnostic tools with higher sensibility and less damage for the patient body, namely on imaging reporters for the management of diseases and optimization of treatment strategies. This article examines the properties of a new class of lanthanide complexes with a tripodal tris-3-hydroxy-4-pyridinone (tris-3,4-HOPO) ligand \u2013 NTP(PrHP)3. Among the studies herein performed, major relevance is given to the thermodynamic stability of the complexes with a series of Ln3+ ions (Ln = La, Pr, Gd, Er, Lu) and to the magnetic relaxation properties of the Gd3+ complex. This hexadentate ligand enables the formation of (1 : 1) Ln3+ complexes with high thermodynamic stability following the usual trend, while the Gd-chelates show improved relaxivity (higher hydration number), as compared with the commercially available Gd-based contrast agents (CAs); transmetallation of the Gd3+\u2013L complex with Zn2+ proved to be thermodynamically and kinetically disfavored. Therefore, NTP(PrHP)3 emerges as part of a recently proposed new generation of CAs with prospective imaging sensibility gains