Metal complexes for the visualisation of amyloid peptides

Abstract

Amyloid forms of many different proteins have been long identified as relevant biomarkers in important pathologies with high societal impact, including A in Alzheimer’s disease, amylin in type 2 diabetes,...

A closer look at amyloid ligands, and what they tell us about protein aggregates

“…We compiled a database of 3457 measurements of ligand–amyloid fibril interactions from the scientific literature. 50–385 The requirements to be included in this database were (1) a known chemical structure, (2) a structure that does not contain metals (metalloligands have been thoroughly reviewed elsewhere in the literature 43,386–391 ), (3) a K d or IC 50 measurement, and (4) a fibril target related to Aβ, tau, or αSyn. Nearly half of the database reports on binding to Aβ fibrils formed in vitro , although recent years has seen a shift in focus toward tau and αSyn fibrils formed in vitro (Table 1).…”

Solid-Phase Synthesis of 2-Benzothiazolyl and 2-(Aminophenyl)benzothiazolyl Amino Acids and Peptides

“…2-phenylbenzothiazoles have also shown interesting metal-involved noncovalent interactions [ 27 , 28 , 29 , 30 ] with broad applications in materials science, while in the diagnostic area, many metal-radiolabeled 2-phenylbenzothiazole derivatives are continuing to be explored as amyloid imaging agents [ 23 , 31 , 32 , 33 ]. Non-metal-based positron emission tomography (PET) imaging of Aβ plaques is also possible through the use of radiolabeled benzothiazoles such as the 18 F-labeled derivative of 2-(4-aminophenyl)benzothiazole [ 18 F] Flutemetamol, which gained approval in 2013 for clinical use [ 34 , 35 ].…”

“…The condensation of 2-(4-aminophenyl)benzothiazole with amino acids has been achieved by its reaction with 1-hydroxybenzotriazole activated amino acids [25]. Besides the limitations of the ap plied chemistries during 2-(4-aminophenyl)benzothiazole synthesis (high temperatures complex product mixtures, substrate dependence) and the conjugation of 2-(4-aminophe nyl)benzothiazole with 1-hydroxybenzotriazolyl amino acids (low reactivity, repeated 2-phenylbenzothiazoles have also shown interesting metal-involved noncovalent interactions [27][28][29][30] with broad applications in materials science, while in the diagnostic area, many metal-radiolabeled 2-phenylbenzothiazole derivatives are continuing to be explored as amyloid imaging agents [23, [31][32][33]. Non-metal-based positron emission tomography (PET) imaging of Aβ plaques is also possible through the use of radiolabeled benzothiazoles such as the 18 F-labeled derivative of 2-(4-aminophenyl)benzothiazole [ 18 F] Flutemetamol, which gained approval in 2013 for clinical use [34,35].…”

Pentadentate and Hexadentate Pyridinophane Ligands Support Reversible Cu(II)/Cu(I) Redox Couples

“…Mononuclear copper complexes have been extensively utilized throughout various areas of inorganic chemistry: synthesis of structural or functional biomimetic inorganic complexes of Cu-containing enzymes [1][2][3][4], cation detection or sequestration [5,6], development of metal-based therapeutic or diagnostic compounds [7][8][9][10], and many others. In particular, the development of 64 Cu-based positron emission tomography (PET) agents has garnered significant attention in recent years as an alternative to shorter-lived radionuclides 11 C and 18 F, which are commonly used in PET imaging [11][12][13]. However, these 64 Cu PET agents still face challenges presented by the possibility of in vivo decomplexation.…”