22 research outputs found

    Microfluidic Print-to-Synthesis Platform for Efficient Preparation and Screening of Combinatorial Peptide Microarrays

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    In this paper, we introduce a novel microfluidic combinatorial synthesis platform, referred to as Microfluidic Print-to-Synthesis (MPS), for custom high-throughput and automated synthesis of a large number of unique peptides in a microarray format. The MPS method utilizes standard Fmoc chemistry to link amino acids on a polyethylene glycol (PEG)-functionalized microdisc array. The resulting peptide microarrays permit rapid screening for interactions with molecular targets or live cells, with low nonspecific binding. Such combinatorial peptide microarrays can be reliably prepared at a spot size of 200 μm with 1 mm center-to-center distance, dimensions that require only minimal reagent consumption (less than 30 nL per spot per coupling reaction). The MPS platform has a scalable design for extended multiplexibility, allowing for 12 different building blocks and coupling reagents to be dispensed in one microfluidic cartridge in the current format, and could be further scaled up. As proof of concept for the MPS platform, we designed and constructed a focused tetrapeptide library featuring 2560 synthetic peptide sequences, capped at the N-terminus with 4-[(<i>N</i>′-2-methylphenyl)­ureido]­phenylacetic acid. We then used live human T lymphocyte Jurkat cells as a probe to screen the peptide microarrays for their interaction with α4β1 integrin overexpressed and activated on these cells. Unlike the one-bead-one-compound approach that requires subsequent decoding of positive beads, each spot in the MPS array is spatially addressable. Therefore, this platform is an ideal tool for rapid optimization of lead compounds found in nature or discovered from diverse combinatorial libraries, using either biochemical or cell-based assays

    Imaging of dogs with lymphoma using <sup>99m</sup>Tc-LLP2A-HYNIC-PEG and <sup>99m</sup>Tc-LLP2A-HYNIC.

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    <p>A. Lateral image of the head at 4 h. Mandibular lymph node activity (arrow) in a dog with lymphoma imaged with <sup>99m</sup>Tc-LLP2A-HYNIC-PEG. The parotid salivary gland (P) has normal uptake. B. Ventrodorsal projection of the mid-abdomen with head at top of image at 4 h. Renal uptake (white *) in a kidney affected with lymphoma using <sup>99m</sup>Tc-LLP2A-HYNIC. C. Lateral pre-chemotherapy of the liver (outlined) of the same dog as in A, with head to the left. D. Post chemotherapy, the liver is smaller and has less activity. There is activity visible in the stomach (black *).</p

    Bioinspired Screening of Anti-Adhesion Peptides against Blood Proteins for Intravenous Delivery of Nanomaterials

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    Nanomaterials (NMs) inevitably adsorb proteins in blood and form “protein corona” upon intravenous administration as drug carriers, potentially changing the biological properties and intended functions. Inspired by anti-adhesion properties of natural proteins, herein, we employed the one-bead one-compound (OBOC) combinatorial peptide library method to screen anti-adhesion peptides (AAPs) against proteins. The library beads displaying random peptides were screened with three fluorescent-labeled plasma proteins. The nonfluorescence beads, presumed to have anti-adhesion property against the proteins, were isolated for sequence determination. These identified AAPs were coated on gold nanorods (GNRs), enabling significant extension of the blood circulating half-life of these GNRs in mice to 37.8 h, much longer than that (26.6 h) of PEG-coated GNRs. In addition, such AAP coating was found to alter the biodistribution profile of GNRs in mice. The bioinspired screening strategy and resulting peptides show great potential for enhancing the delivery efficiency and targeting ability of NMs