Sensitive Structural Control of Macrocycle Threading by a Fluorescent Squaraine Dye Flanked by Polymer Chains

Liu, Wenqi; Peck, Evan M.; Hendzel, Kevin D.; Smith, Bradley D.

doi:10.1021/acs.orglett.5b02633

Cited by 28 publications

(55 citation statements)

References 23 publications

(20 reference statements)

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“…Systematic structural studies have evaluated the change in K a and association kinetics as a function of dye structure and uncovered two interesting trends. 48 One is that attachment of long polyethylene glycol chains to the nitrogen atoms at each end of the dye structures has virtually no effect on K a or k on . But k on is greatly affected by the steric size of the second N -substituent attached to each dye termini.…”

Section: Host•guest Mimics Of Biotin/(strept)avidinmentioning

confidence: 99%

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Synthetic mimics of biotin/(strept)avidin

et al. 2017

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Biotin/(strept)avidin self-assembly is a powerful platform for nanoscale fabrication and capture with many different applications in science, medicine, and nanotechnology. However, biotin/(strept)avidin self-assembly has several well-recognized drawbacks that limit performance in certain technical areas and there is a need for synthetic mimics that can either become superior replacements or operational partners with bio-orthogonal recognition properties. The goal of this tutorial review is to describe the recent progress in making high affinity synthetic association partners that operate in water or biological media. The review starts with a background summary of biotin/(strept)avidin self-assembly and the current design rules for creating synthetic mimics. A series of case studies are presented that describe recent success using synthetic derivatives of cyclodextrins, cucurbiturils, and various organic cyclophanes such as calixarenes, deep cavitands, pillararenes, and tetralactams. In some cases, two complementary partners associate to produce a nanoscale complex and in other cases a ditopic host molecule is used to link two partners. The article concludes with a short discussion of future directions and likely challenges.

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Section: Host•guest Mimics Of Biotin/(strept)avidinmentioning

confidence: 99%

“…( bottom ) Pre-assembly of near-infrared fluorescent molecular probes with multivalent affinity for bone surfaces. (Adapted with permission from ref 48 and 49. Copyright 2016, American Chemical Society).…”

Section: Figurementioning

confidence: 99%

Synthetic mimics of biotin/(strept)avidin

et al. 2017

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“…7,8 In an effort to address this deficiency, we are developing a programmable self-assembly synthesis method that can produce libraries of targeted near-infrared fluorescent probes with multiple targeting ligands. 9,10 We refer to the basic self-assembly process as Synthavidin (Synthetic Avidin) technology. 11 To briefly summarize, a tetralactam macrocycle with appended targeting ligands is threaded onto a fluorescent squaraine scaffold S that is flanked by polyethylene glycol (PEG) chains to give a pre-assembled fluorescent probe (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Preassembled Fluorescent Multivalent Probes for the Imaging of Anionic Membranes

et al. 2017

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A new self-assembly process known as Synthavidin (Synthetic Avidin) technology was used to prepare targeted probes for near-infrared fluorescence imaging of anionic membranes and cell surfaces, a hallmark of many different types of disease. The probes were pre-assembled by threading a tetralactam macrocycle with six appended zinc-dipicolylamine (ZnDPA) targeting units onto a linear scaffold with one or two squaraine docking stations to produce hexavalent or dodecavalent fluorescent probes. A series of liposome titration experiments showed that multivalency promoted stronger membrane binding by the dodecavalent probe. In addition, the dodecavalent probe exhibited turn-on fluorescence due to probe unfolding during fluorescence microscopy at the membrane surface. But the dodecavalent probe also had a higher tendency to self-aggregate after membrane binding leading to probe self-quenching under certain conditions. This self-quenching effect was apparent during fluorescence microscopy experiments that recorded low fluorescence intensity from anionic dead and dying mammalian cells that were saturated with the dodecavalent probe. Conversely, probe self-quenching was not a factor with anionic microbial surfaces where there was intense fluorescence staining by the dodecavalent probe. A successful set of rat tumor imaging experiments confirmed that the pre-assembled probes have sufficient mechanical stability for effective in vivo imaging. The results demonstrate the feasibility of this general class of pre-assembled fluorescent probes for multivalent targeting, but fluorescence imaging performance depends on the specific physical attributes of the biomarker target such as the spatial distance between different copies of the biomarker and the propensity of the probe/biomarker complex to self-aggregate.

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“…To date, we have pre‐assembled fluorescent molecular probes that selectively target bone, dead/dying mammalian tissue, and various microbial species . One of the major advantages of Synthavidin self‐assembly is the capability of forming threaded complexes with long PEG chains appended to the ends of the squaraine dye . This means the length of the PEG chains is a structural parameter that can be systematically varied in order to optimize the pharmacokinetic properties of the pre‐assembled probes.…”

Section: Introductionmentioning

confidence: 99%

Non‐Covalent Assembly Method that Simultaneously Endows a Liposome Surface with Targeting Ligands, Protective PEG Chains, and Deep‐Red Fluorescence Reporter Groups

Shaw

Liu

Brennan

et al. 2017

Chemistry A European J

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A new self-assembly method is used to rapidly functionalize the surface of liposomes without perturbing the membrane integrity or causing leakage of the aqueous contents. The key molecule is a cholesterol-squaraine-PEG conjugate with three important structural elements: a cholesterol membrane anchor, a fluorescent squaraine docking station that allows rapid and high-affinity macrocycle threading, and a long PEG-2000 chain to provide steric shielding of the decorated liposome. The two-step method involves spontaneous insertion of the conjugate into the outer leaflet of pre-formed liposomes followed by squaraine threading with a tetralactam macrocycle that has appended targeting ligands. A macrocycle with six carboxylates permitted immobilization of intact fluorescent liposomes on the surface of cationic polymer beads, whereas a macrocycle with six zinc(II)-dipicolylamine units enabled selective targeting of anionic membranes, including agglutination of bacteria in the presence of human cells.

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Sensitive Structural Control of Macrocycle Threading by a Fluorescent Squaraine Dye Flanked by Polymer Chains

Cited by 28 publications

References 23 publications

Synthetic mimics of biotin/(strept)avidin

Synthetic mimics of biotin/(strept)avidin

Preassembled Fluorescent Multivalent Probes for the Imaging of Anionic Membranes

Non‐Covalent Assembly Method that Simultaneously Endows a Liposome Surface with Targeting Ligands, Protective PEG Chains, and Deep‐Red Fluorescence Reporter Groups

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