High-Throughput Screening of Small Molecule Ligands Targeted to Live Bacteria Surface

Lee, Jeong Heon; Park, Sunny; Hyun, Hoon; Bordo, Mark W.; Oketokoun, Rafiou; Nasr, Khaled; Frangioni, John V.; Choi, Hak

doi:10.1021/ac303199x

Cited by 11 publications

(14 citation statements)

References 23 publications

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“…NIR Fluorescent Contrast Agents: Methylene blue (MB; USP 1%, 10 mg/mL) was purchased from Taylor Pharmaceuticals (Decatur, IL). T700-H and T700-F were synthesized as described in our previous reports 12 , 18 - 20 , and served as pancreas targeting 700 nm emitting NIR fluorophores. Three different 800 nm NIR fluorophores including ZW800-1, ZW800-3C, and ESNF31, were also used for the dual channel imaging of surrounding tissue: ZW800-1 for NIR angiography and kidney imaging 21 ; ZW800-3C for PLN imaging 13 , and ESNF31 for adrenal glands 15 .…”

Section: Methodsmentioning

confidence: 99%

Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery

Wada¹,

Hyun²,

Vargas³

et al. 2015

Theranostics

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Objective: Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury.Design: After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.Results: T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR ≥ 2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time.Conclusion: Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

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Section: Methodsmentioning

confidence: 99%

Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery

Wada¹,

Hyun²,

Vargas³

et al. 2015

Theranostics

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“…With a median deposit accuracy of 97% and plate processing time of 11 minutes, the bead sorting station can process over twenty plates or approximately 8,500 beads in under five hours. When incorporated into a high-throughput small molecule synthesis and screening program, 14–16 the instrument we describe has the potential to accelerate drug development and high-throughput screening.…”

Section: Resultsmentioning

confidence: 99%

High-Throughput Sorting and Placement of One-Bead–One-Compound (OBOC) Libraries from Bulk to Single Wells in Organic Solvent

et al. 2015

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One-bead-one-compound (OBOC) solid-phase combinatorial chemistry has been used extensively in drug discovery. However, a major bottleneck has been the sorting of individual beads, while still swollen in organic solvent, into individual wells of a microwell plate. To solve this problem we have constructed an automated bead sorting system with integrated quality control that is capable of sorting and placing large numbers of beads in bulk to single wells of a 384-well plate, all in organic solvent. The bead sorter employs a unique, reciprocating fluidic design capable of depositing 1 bead per 1.5 s with an average accuracy of 97%. We quantified the performance of this instrument by sorting over 8,500 beads followed by cleaving the conjugated compound and confirming the chemical identity of each by LC/MS. This instrument should enable more efficient screening of combinatorial small molecule libraries without the need to dry beads or otherwise change chemical environment.

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“…Finally, Lee et al developed an SMM platform to identify small molecules that bind to the surface of live pathogenic bacteria [40]. Small molecules were first immobilized on amine-reactive functionalized microarray slide with PEG-linker.…”

Section: Probe Discoverymentioning

confidence: 99%

Recent discoveries and applications involving small-molecule microarrays

Hong

Neel

Wassaf

et al. 2014

Current Opinion in Chemical Biology

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High-throughput and unbiased binding assays have proven useful in probe discovery for a myriad of biomolecules, including targets of unknown structure or function and historically challenging target classes. Over the past decade, a number of novel formats for executing large-scale binding assays have been developed and used successfully in probe discovery campaigns. Here we review the use of one such format, the small-molecule microarray (SMM), as a tool for discovering protein-small molecule interactions. This review will briefly highlight selected recent probe discoveries using SMMs as well as novel uses of SMMs in profiling applications.

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High-Throughput Screening of Small Molecule Ligands Targeted to Live Bacteria Surface

Cited by 11 publications

References 23 publications

Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery

Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery

High-Throughput Sorting and Placement of One-Bead–One-Compound (OBOC) Libraries from Bulk to Single Wells in Organic Solvent

Recent discoveries and applications involving small-molecule microarrays

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