A Synthetic Membrane-Anchored Antigen Efficiently Promotes Uptake of Antifluorescein Antibodies and Associated Protein A by Mammalian Cells

Hussey, Stephen L.; He, Enfei; Peterson, Blake R.

doi:10.1021/ja017087o

Cited by 28 publications

(40 citation statements)

References 27 publications

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“…8 Intracellular fluorescence was observed in the golgi complex as established by fluorescence colocalization with the golgi-specific red-fluorescent BODIPY TR ceramide probe (Figure 3c).…”

mentioning

confidence: 88%

Sensitive and Rapid Analysis of Protein Palmitoylation with a Synthetic Cell-Permeable Mimic of Src Oncoproteins

Creaser

Peterson

2002

J. Am. Chem. Soc.

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The localization of oncogenic Src and Ras proteins to cellular plasma membranes is critical for the proliferation of specific cancers. In addition to other lipid modifications, these proteins require posttranslational palmitoylation of specific cysteine residues by the enzyme palmitoyl acyltransferase (PAT) in order to be stably anchored at plasma membranes. Hence, the identification of inhibitors of protein palmitoylation has significant potential to define a new class of antitumor agents. However, studies of protein palmitoylation have been hindered by the dynamic and reversible nature of cysteine acylation and the lack of sensitive and convenient assays of PAT activity. To facilitate the rapid identification of compounds that affect protein palmitoylation, we report the solid-phase synthesis of a fluorescent cell-permeable palmitoyl acyltransferase substrate that mimics the N-terminus of Src family proteins. Metabolic radiolabeling and epifluorescence microscopy of Jurkat lymphocytes treated with this Src-mimetic lipopeptide revealed that this compound is palmitoylated intracellularly, which confers localization at cellular plasma membranes. Addition of the palmitoylation inhibitor 2-bromopalmitic acid to substrate-treated cells blocked palmitoylation and diminished substrate-mediated plasma membrane fluorescence. Analysis of inhibition of palmitoylation by flow cytometry revealed that this fluorescent lipopeptide substrate represents a highly sensitive molecular probe of palmitoyl acyltransferase activity that enables unprecedented high-throughput assays of protein palmitoylation.

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“…8 Intracellular fluorescence was observed in the golgi complex as established by fluorescence colocalization with the golgi-specific red-fluorescent BODIPY TR ceramide probe (Figure 3c).…”

mentioning

confidence: 88%

Sensitive and Rapid Analysis of Protein Palmitoylation with a Synthetic Cell-Permeable Mimic of Src Oncoproteins

Creaser

Peterson

2002

J. Am. Chem. Soc.

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“…Intrigued by these observations, we developed a practical method to synthesize multigram quantities of 3β-cholesterylamine,[56] and we have investigated the biological properties of a variety of its derivatives. Some of our early work in this area[57–62] has been reviewed. [63]…”

Section: Cellular Uptake and Trafficking Of Cholesterol-mimetic Mementioning

confidence: 99%

Synthetic cell surface receptors for delivery of therapeutics and probes

Hymel

Peterson

2012

Advanced Drug Delivery Reviews

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Receptor-mediated endocytosis is a highly efficient mechanism for cellular uptake of membrane-impermeant ligands. Cells use this process to acquire nutrients, initiate signal transduction, promote development, regulate neurotransmission, and maintain homeostasis. Natural receptors that participate in receptor-mediated endocytosis are structurally diverse, ranging from large transmembrane proteins to small glycolipids embedded in the outer leaflet of cellular plasma membranes. Despite their vast structural differences, these receptors share common features of binding to extracellular ligands, clustering in dynamic membrane regions that pinch off to yield intracellular vesicles, and accumulation of receptor-ligand complexes in membrane-sealed endosomes. Receptors typically dissociate from ligands in endosomes and cycle back to the cell surface, whereas internalized ligands are usually delivered into lysosomes, where they are degraded, but some can escape and penetrate into the cytosol. Here, we review efforts to develop synthetic cell surface receptors, defined as nonnatural compounds, exemplified by mimics of cholesterol, that insert into plasma membranes, bind extracellular ligands including therapeutics, probes, and endogenous proteins, and engage endocytic membrane trafficking pathways. By mimicking natural mechanisms of receptor-mediated endocytosis, synthetic cell surface receptors have the potential to function as prosthetic molecules capable of seamlessly augmenting the endocytic uptake machinery of living mammalian cells.

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“…Cellular membranes can be chemically altered to facilitate macromolecular uptake. As an example of this Peterson and coworkers [150] have synthesized fluoresceincholesterylamine chimers 144 that enable uptake of antifluorescein antibodies and associated protein complexes by mammalian cells. Recently, the same group has synthesized 7 -substituted -estradiol derivatives bearing side chains terminated with cholesterol and 3 -cholesterylamine 145 (Fig.…”

Section: Cholesterol Based Conjugatesmentioning

confidence: 99%

Steroidal Conjugates and Their Pharmacological Applications

Salunke

Hazra²,

Pore³

2006

CMC

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Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properties. During the past two decades design of such entities has been receiving increasing attention. Among the hybrid natural products, hybrids of steroid frameworks have attracted great attention due to the significant biological properties and numerous therapeutic effects of steroids. The developments made over the past few years in the isolation, design and synthesis of steroidal conjugates and their pharmacological applications are discussed in this review.

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A Synthetic Membrane-Anchored Antigen Efficiently Promotes Uptake of Antifluorescein Antibodies and Associated Protein A by Mammalian Cells

Cited by 28 publications

References 27 publications

Sensitive and Rapid Analysis of Protein Palmitoylation with a Synthetic Cell-Permeable Mimic of Src Oncoproteins

Sensitive and Rapid Analysis of Protein Palmitoylation with a Synthetic Cell-Permeable Mimic of Src Oncoproteins

Synthetic cell surface receptors for delivery of therapeutics and probes

Steroidal Conjugates and Their Pharmacological Applications

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