Fluorine-18 labeling of three novel d-peptides by conjugation with N-succinimidyl-4-[18F]fluorobenzoate and preliminary examination by postmortem whole-hemisphere human brain autoradiography

Treatment with D3 Removes Amyloid Deposits, Reduces Inflammation, and Improves Cognition in Aged AβPP/PS1 Double Transgenic Mice

“…A possible therapeutic invention that has been proposed is interference in the accumulation and deposition of the Aβ protein in aggregates [19, 20]. We have developed a series of D-enantiomeric peptides, using mirror-image phage display techniques, that bind Aβ, with a preference for Aβ 42 [21–26]. We have demonstrated that the small D-enantiomeric peptide D3 (D3-FITC) that specifically precipitates oligomers in a mixture containing monomers and oligomers of Aβ 42 [27] reduces amyloid deposition and decrease cognitive deficits in young Tg AD model mice when they are infused intracerebrally or treated by oral administration [26, 28, 29].…”

Biotechnologically engineered protein binders for applications in amyloid diseases

“…Published K D -values for peptides with sequence homology and gammabodies range from 300 nM to 1.4 mM for gammabodies binding to fibrils [12], !37 mM for KLVFFderived peptides binding to Ab(10-35)-amide [28], 0.4 mM for peptide D1 binding to Ab(1-42) [29], 180 AE 90 nM for tritium labeled KLVFF-KKKKKK binding to Ab protofibrils [30], and 17.5 nM for di-methylated full-length islet amyloid polypeptide (IAPP) binding to fluorescently labeled IAPP [31].…”

“…Many have been explored for the detection of amyloid structures formed in vitro [8,10,21,27,32] and of amyloid deposits in histological sections from biopsy material [9,25,29,35]. Detection may depend on secondary antibodies or related tools, but biotechnological binders can easily be functionalized, as was shown for fluorescently labeled D3 peptide, which directly visualizes plaques in AD mouse models upon intracerebral infusion [25], or genetic coupling of antibody fragments B10 and KW1 to E. coli alkaline phosphatase (AP) to enable ELISA, spot blot, or histology applications with phosphatase reagents.…”

Improved synthesis of [18F]FS-PTAD as a new tyrosine-specific prosthetic group for radiofluorination of biomolecules

“…Among all indirect radiofluorination methods, there are a few commonly used 18 F-prosthetic groups such as N-succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB) (Mading et al, 2005;Vaidyanathan and Zalutsky, 2006;Jahan et al, 2012); 4-nitrophenyl-2-[ 18 F]fluoropropionate ([ 18 F]NPE) (Guhlke et al, 1994;Chin et al, 2012); 6-[ 18 F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([ 18 F]FPyTFP) (Olberg et al, 2010;Malik et al, 2011) and [ 18 F]2-cyanobenzothiazole ([ 18 F]CBT) (Jeon et al, 2012;Su et al, 2014).…”