Tuning the stereo-hindrance of a curcumin scaffold for the selective imaging of the soluble forms of amyloid beta species

Li, Yuyan; Yang, Jian; Liu, Hongwu; Yang, Jing; Du, Lei; Feng, Haiwei; Tian, Yanli; Cao, Jianqin; Ran, Chongzhao

doi:10.1039/c7sc02050c

Cited by 84 publications

(95 citation statements)

References 43 publications

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“…Over the past several years, we have synthesized numerous curcumin analogues CRANAD-Xs. 24 To investigate whether these analogues have similar a effect as CRANAD-17, we used the SPEED to test CRANAD-Xs (X= -3, -25, -44 and -102) ( Supplementary Fig.8,9). We found that these compounds could alter the 4G8 antibody recognition and lead to increased chemilumiescence intensity.…”

Section: Resultsmentioning

confidence: 99%

“…CRANAD-Xs compounds were synthesized according to our previously reported procedures and compounds with purities more than 95% determined by analytical HPLC, were used for further evaluation. 17,24 Synthetic Aβ1-40 peptide was purchased from rPeptide and different forms of Aβ1-40 including monomer, oligomer and aggregate were prepared by our previously reported methods. 17 In Vivo Anti-inflammation Test in Transgenic Mice.…”

Section: Methodsmentioning

confidence: 99%

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A screening platform based on epitope editing for drug discovery

Zhu

Yang

Van

et al. 2019

Preprint

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The interaction between an antibody and its epitope has been daily utilized in various biological studies; however it has been rarely explored whether small molecules can alter the interaction. We discovered that small molecules could alter/edit surface properties of amyloid beta (Aβ) epitopes, and consequently inhibit or enhance corresponding antibody recognition. Remarkably, this editing effect could generate functional changes including protein aggregation behaviors, cell cytokine secreting and in vivo microglia activation. According to this discovery, we proposed a screen 2 platform based on epitope editing for drug discovery (SPEED). With a small library of compounds, we validated that SPEED could be used to seek new leads for Aβ species.We also demonstrated that this platform could potentially be extended to other targets including tau protein and PD-L1 protein. The SPEED is a simple, fast and label-free screening method. We believe that the SPEED strategy could be universally applicable for seeking and validating drug candidates and imaging ligands.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A screening platform based on epitope editing for drug discovery

Zhu

Yang

Van

et al. 2019

Preprint

Self Cite

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“…[61] The probe exhibited an ideal fluorescence absorption and emission at 630 and 750 nm, respectively. [63] Boron dipyrromethane (BODIPY) has attracted wide attention for its excellent optical properties and applications in biological imaging. More importantly, CRANAD-58 was capable of targeting soluble Aβ in vivo from 4-month-old APP/PS1 transgenic mouse.…”

Section: The Detection Of Aβ Oligomersmentioning

confidence: 99%

“…The probe CRANAD‐102 exhibits higher selectivity toward Aβ oligomers over Aβ aggregates both in solution and in vivo. Furthermore, this molecule could penetrate the BBB to detect Aβ oligomers at an early stage of AD …”

Section: The Fluorescence Detection Of Aβmentioning

confidence: 99%

Fluorescence Detection and Dissociation of Amyloid‐β Species for the Treatment of Alzheimer's Disease

Shen

Zheng

et al. 2019

Advanced Therapeutics

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Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disease. It is well established that the β-amyloid peptide (Aβ) species existing in several forms, such as soluble monomers, oligomers, and insoluble aggregates, play an essential role in the pathophysiology of AD. Therefore, much effort has been made to specifically detect Aβ species and to inhibit Aβ aggregation for the treatment of AD. In this review, an overview of recent advances in detecting different Aβ forms mainly containing Aβ aggregates, Aβ oligomers, and Aβ protofibrils is provided. In addition, photodynamic therapy (PDT) and photothermal therapy (PTT) are considered to be promising modalities for the treatment of AD because of the minimal invasiveness and high spatial selectivity. Herein, the strategies of inhibiting Aβ aggregation and dissociating Aβ aggregates using PDT, PTT, and Aβ inhibitors for the treatment of AD are summarized.

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“…Optical imaging, including NIRF imaging and two-photon imaging, are the most used methods for preclinical investigations of fundamental pathological questions and for therapy monitoring in drug development. In the past years, our group has developed a series of smart NIRF probes, CRANAD-X for Abs [38][39][40][41][42][43] , and numerous other "smart" (turn-on) fluorescence probes have also been reported 28,37,[44][45][46][47][48][49][50][51][52][53][54][55][56][57] . However, "smart" chemiluminescence probes are rare 58 and none has been applied for studying Abs.…”

Section: Introductionmentioning

confidence: 99%

Smart Chemiluminescence Probes and Dual-Amplification of Signal for Detection of Amyloid Beta Species in Alzheimer’s Disease Model

Yang¹,

Yin²,

Van³

et al. 2020

Preprint

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<div>Fluorescence and chemiluminescence imaging are the most widely applied optical emissive imaging</div><div>methods in biomedical research. “Smart” (turn-on) fluorescence imaging has been routinely used for in</div><div>vitro, cellular, and in vivo imaging; however, smart chemiluminescence imaging has been rarely explored.</div><div>In this report, we designed chemiluminescence probe ADLumin-1 and validated that ADLumin-1 was a</div><div>smart chemiluminescence probe for amyloid beta (Ab) species, evidenced by a 216-fold amplification of</div><div>chemiluminescence intensity upon mixing with Abs in vitro. In vivo two photon imaging indicated that</div><div>ADLumin-1 could efficiently cross blood-brain- barrier (BBB) and provided excellent contrast both for Ab</div><div>plaques and cerebral amyloid angiopathy (CAA). In vivo whole brain imaging showed that the</div><div>chemiluminescence signal of ADLumin-1 from 5-month-old transgenic AD (5xFAD) mice was 1.80-fold</div><div>higher than that from the age-matched wild-type mice. Moreover, we demonstrated that it was feasible to</div><div>further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two</div><div>non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo</div><div>whole brain imaging. Our results showed that DAS-CRET could provide a 2.25-fold margin between 5-</div><div>month-old 5xFAD mice and wild type mice. To our knowledge, this is the first report that a</div><div>chemiluminescence probe could be used for detecting Ab species both in vitro and in vivo. Although</div><div>ADLumin-1 was designed for Abs, we believe that our strategy could be potentially extended to a wide</div><div>range of targets, including other aggregating-prone proteins. Notably, our results suggested that the</div><div>strategies for turning-on fluorescence could be used for amplifying chemiluminescence, and we believe that</div><div>our studies could inspire considerably more research on chemiluminescence imaging</div>

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Tuning the stereo-hindrance of a curcumin scaffold for the selective imaging of the soluble forms of amyloid beta species

Abstract: We demonstrate that tuning the stereo-hindrance of the phenoxy-alkyl chains at the 4-position of a curcumin scaffold could lead to certain selectivity for soluble Aβs over insoluble Aβs.

Cited by 84 publications

References 43 publications

A screening platform based on epitope editing for drug discovery

A screening platform based on epitope editing for drug discovery

Fluorescence Detection and Dissociation of Amyloid‐β Species for the Treatment of Alzheimer's Disease

Smart Chemiluminescence Probes and Dual-Amplification of Signal for Detection of Amyloid Beta Species in Alzheimer’s Disease Model

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