A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications

Suazo, Kiall F.; Park, Keun‐Young; Distefano, Mark D.

doi:10.1021/acs.chemrev.0c01108

Cited by 83 publications

(88 citation statements)

References 563 publications

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“…1A. [28][29][30] Prenylomic analysis using C15AlkOPP, and related compounds, have been employed to identify and track the levels of specific prenylated proteins in cell culture-based systems and to explore their roles in diseases including cancer. [31][32][33][34] In earlier work, this method was used to profile prenylated proteins in brain-derived cell lines using both primary and immortalized cells.…”

Section: Mainmentioning

confidence: 99%

In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins

Jeong

Auger

Maity

et al. 2022

Preprint

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Dysregulation of protein prenylation has been implicated in many diseases, including Alzheimer's disease (AD). Prenylomic analysis, the combination of metabolic incorporation of an isoprenoid analogue (C15AlkOPP) into prenylated proteins with a bottom-up proteomic analysis, has allowed identification of prenylated proteins in various cellular models. Here, transgenic AD mice were administered with C15AlkOPP through intracerebroventricular (ICV) infusion over 13 days. Using prenylomic analysis, 36 prenylated proteins were enriched in the brains of AD mice. Importantly, the prenylated forms of 15 proteins were consistently upregulated in AD mice compared to non-transgenic wild-type controls. These results highlight the power of this in vivo metabolic labeling approach to identify multiple post-translationally modified proteins that may serve as potential therapeutic targets for a disease that has proved refractory to treatment thus far. Moreover, this method should be applicable to many other types of protein modifications, significantly broadening its scope.

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Section: Mainmentioning

confidence: 99%

In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins

Jeong

Auger

Maity

et al. 2022

Preprint

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“…The majority of the studies on protein prenylation concentrate on farnesylated and geranylgeranylated proteins and developing the suitable tools. 24 …”

Section: Overview Of Superfamily Of Small Gtpases and Enzymes Within The Mevalonate Pathwaymentioning

confidence: 99%

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

2021

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A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein–protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Hyperglycemia-induced upregulation of small GTPases suggests that inhibition of these pathways deserves to be considered as a potential therapeutic approach in treating T2D. This Perspective presents how inhibition of various points in the mevalonate pathway might affect protein prenylation and functioning of diabetes-affected tissues and contribute to chronic inflammation involved in diabetes mellitus (T2D) development. We also demonstrate the currently available molecular tools to decipher the mechanisms linking the mevalonate pathway’s enzymes and GTPases with diabetes.

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“…In addition, by varying the concentration of the farnesyl-CSANs on the sender cells, induced interactions between the sender and receiver cells could be kept at a minimum, thus reducing the effect of the modification on natural or engineered interactions between the sender and receiver cells. Moreover, by incorporating the azide-functionalized farnesyl analogs as bioconjugation handles 31 , both the apoptosis inducing drug, MMAE, and antisense oligonucleotide targeting expression of the translation initiation factor, eIF4E, were able to undergo C4T transfer (Fig. 1c).…”

Section: Introductionmentioning

confidence: 99%

Macro-Chemical Biology: Engineering Biomimetic Trogocytosis with Farnesylated Chemically Self-Assembled Nanorings

Wang

Rozumalski

Lichtenfels

et al. 2022

Preprint

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With the recent success of cell-based therapies, there has been a rapidly emerging interest in the engineering of cell-cell interactions and communications. Inspired by the natural intercellular material transfer process of trans-endocytosis or trogocytosis, we proposed that targeted farnesylated chemically self-assembled nanorings (farnesyl-CSANs) could serve as a biomimetic trogocytosis vehicle for engineering directional cargo transfer between cells; thus, allowing cell-cell interactions to be monitored, as well as facilitating communication between the cells by delivery of bioactive species. The membranes of sender cells were stably modified by hydrophobic insertion with the targeted farnesyl-CSANs and to be efficiently transferred to receiver cells expressing the appropriate receptor by endocytosis. CSAN-assisted cell-cell cargo transfer (C4T) was demonstrated to be receptor-specific and dependent on direct cell-cell interactions, the rate of receptor internalization and the amount of receptor expression. In addition, C4T was shown to facilitate cell-to-cell delivery of an apoptosis inducing drug, as wells as antisense oligonucleotides (ASO). Taken together, the C4T approach is a potentially versatile biomimetic trogocytosis platform that can be used to monitor cell-cell interactions, as well as the engineering of cell-cell communications, such as cell-based drug delivery.

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A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications

Cited by 83 publications

References 563 publications

In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins

In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

Macro-Chemical Biology: Engineering Biomimetic Trogocytosis with Farnesylated Chemically Self-Assembled Nanorings

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