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Cell-Penetrating Peptides pp 259–275Cite as

Pharmacology, Biodistribution, and Efficacy of GPCR-Based Pepducins in Disease Models

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 683))

Abstract

G protein-coupled receptors (GPCR) are a superfamily of receptors that are vital in a wide array of physiological processes. Modulation of GPCR signaling has been an intensive area of therapeutic study, mainly due to the diverse pathophysiological significance of GPCRs. Pepducins are cell-penetrating lipidated peptides designed to target the intracellular loops of the GPCR of interest. Pepducins can function as agonists or antagonists of their cognate receptor, making them highly useful compounds for the study of GPCR signaling. Pepducins have been used to control platelet-dependent hemostasis and thrombosis, tumor growth, invasion, and angiogenesis, as well as to improve sepsis outcomes in mice. Pepducins have been successfully designed against a wide variety of GPCRs including the protease-activated receptors (PAR1, 2, 4), the chemokine receptors (CXCR1, 2, 4), the sphingosine-1-phosphate receptor (S1P3), the adrenergic receptor (ADRA1B), and have the potential to help reveal the functions of intractable GPCRs. Pharmacokinetic, pharmacodynamic, and biodistribution studies have showed that pepducins are widely distributed throughout the body except the brain and possess appropriate drug-like properties for use in vivo. Here, we discuss the delivery, pharmacology, and biodistribution of pepducins, as well as the effects of pepducins in models of inflammation, cardiovascular disease, cancer, and angiogenesis.

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Acknowledgments

This research was supported by NIH grants CA104406 (L. Covic) and CA122992, HL64701, and HL57905 (A. Kuliopulos).

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Authors and Affiliations

  1. Tufts Medical Center, Molecular Oncology Research Institute, Boston, MA, USA

    Sarah L. Tressel, Georgios Koukos, Boris Tchernychev & Suzanne L. Jacques

  2. Tufts Medical Center, and Departments of Biochemistry and Medicine, Tufts University School of Medicine, Molecular Oncology Research Institute, Boston, MA, USA

    Lidija Covic & Athan Kuliopulos

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  1. Sarah L. Tressel
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  2. Georgios Koukos
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  3. Boris Tchernychev
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  4. Suzanne L. Jacques
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  5. Lidija Covic
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  1. , Department of Neurochemistry, Stockholm University, Svante Arrheniusv 21A21A, Stockholm, 106 91, Sweden

    Ülo Langel

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Tressel, S.L., Koukos, G., Tchernychev, B., Jacques, S.L., Covic, L., Kuliopulos, A. (2011). Pharmacology, Biodistribution, and Efficacy of GPCR-Based Pepducins in Disease Models. In: Langel, Ü. (eds) Cell-Penetrating Peptides. Methods in Molecular Biology, vol 683. Humana Press. https://doi.org/10.1007/978-1-60761-919-2_19

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  • DOI: https://doi.org/10.1007/978-1-60761-919-2_19

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