Novel D–A–D based near-infrared probes for the detection of β-amyloid and Tau fibrils in Alzheimer's disease

Abstract

Novel D-π-A-π-D probes were investigated for the detection of Aβ plaques and NFTs. The probes displayed remarkable optical properties, and DADNIR-2 possessed high affinity towards Tau and Aβ aggregates (Kd = 0.41 nM and 1.04 nM, respectively) with certain selectivity. DADNIR-2 could penetrate the BBB and label Aβ plaques in vivo.

Rational Design and Synthesis of a Novel BODIPY-based Probe for Selective Imaging of Tau Tangles in Human iPSC-derived Cortical Neurons

“…It has to be noticed that while previous reports 31,42 , indicated that the emission wavelength of TAU1 is >650 nm, prior to perform measurements on iPSC derived cortical neurons we measured excitation/emission spectra for both BT1 and TAU1 using the experimental conditions suitable for neuronal tau imaging and we found different results. This discrepancy may arise from different solution buffer conditions.…”

“…Here, we designed a small-size focused library of uorescent probes consisting of a BODIPY core (electron acceptor) featuring a highly conjugated system ending with an aliphatic amine (electron donor) with a length in the range 13-19 Å, and characterized by a different polarity. This structural modi cation were rationally designed to improve the P-tau vs Aβ selectivity respect to TAU1, that has been shown to bind also Aβ 42 , and the small-size focused library was docked toward the 6-mer model of the PHF6 fragment, present in the R3 region of the P-tau protein and responsible for the propensity of the protein itself to assemble into brils. Among the most promising probes in terms of binding mode, theoretical a nity and polarity, BT1 has been synthesized and tested in vitro onto human iPSC-derived NGN2-induced neuronal cell cultures, which represent a reliable system for modeling human neurological disorders, including AD.…”

Sensing Performance Investigations on Two-Photon Fluorescent Probes for Detecting β-Amyloid in Alzheimer’s Disease

“…A potential route to identify efficient two-photon sensors for β-amyloid imaging is to explore the two-photon properties of the dyes that have already shown some success in this aspect. Up to now, plenty of fluorescent probes with multiple chemical structures have been synthesized and experimentally applied to detect the β-amyloid plaques in vivo, such as PAD-1, DCIP-1, and BAP-1 with donor-acceptor architecture [16][17][18], and QAD1, DADNIR-2, and CRANAD-3 with donor-acceptor-donor architecture [19][20][21]. Due to some correlations between the donor-π-acceptor structural compounds and their optical properties that have already been established [22,23], we choose molecules with the N,N-dimethylamino group as the donor and dicyano group as the acceptor to study their possibility to be two-photon fluorescent probes for detecting β-amyloid.…”

Fluorescent Diagnostic Probes in Neurodegenerative Diseases

“…Li et al also architected a series of molecules for detecting β‐amyloid and Tau fibrils, DADNIRs, with a D–π–A–π–D structure (Figure 8D) bridged by a conjugated π system and designed by an electron‐rich donor (D) and an electron‐deficient acceptor (A), which pushed the fluorescence emission into the NIR region. [ 60 ] Herein, N,N ‐dimethylamino and methoxy groups were used as the donor and cyano groups were used as the acceptor; polyenic chains with different lengths with good ICT characteristics were used as π‐bridges. The maximum emission of DADNIRs suggested that the D–π–A–π–D scaffold was better at pushing the emission into the NIR region, than the D–π–A structure.…”