Protein Kinase C: synthesis of a C1-domain binding compound as an immobilizable tool for affinity chromatography

Research output: ThesisMaster's thesisTheses

Abstract

Protein kinase C (PKC) belongs to the AGC family of serine/threonine kinases and plays a critical role in the regulation of various aspects of cell functions, including growth, differentiation, metabolism and apoptosis. PKC isoenzymes, as one of the main mediator to convert the extracellular stimuli into biological responses, are activated by phospholipid-derived second messengers and transmit their signal by phosphorylating specific protein substrates. Since protein kinase C is involved in a wide range of signal transduction networks, it represents an interesting and extensively studied molecular target for the treatment of several diseases, such as cancer, and Alzheimer’s disease.
Prof. Jari Yli-Kauhaluoma and his team of researchers have been interested in developing simple hydrophobic isophthalic acid derivatives able to modify PKC functions by targeting the C1 domain of the enzyme. A set of small derivatives have been rationally designed and synthesized with a structure-based approach, using the crystal structure of the PKCδ C1B domain. The bis[3-(trifluoromethyl)benzyl] 5-(hydroxymethyl)isophthalate has been selected for further studies due to its high affinity for the C1 domain of PKCα and –δ.

The aim of the thesis was to synthesize a new molecule that preserves the scaffold structure of the previous synthesized PKC C1-domain binding compound with a polyethyleneglycol linker attached to it. This new compound will be used as a research tool in affinity chromatography in order to conduct affinity studies and to achieve reliable knowledge on other potential target(s) than PKCs, which could be found in the cell lysate. Furthermore, the future study can provide important clues about the physiological effect of the original ligand on the cell. The work was carried out in the Medicinal Chemistry group of the Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki (Finland).
Original languageEnglish
Publisher
Publication statusPublished - 2012
MoE publication typeG2 Master's thesis, polytechnic Master's thesis

Fields of Science

  • 317 Pharmacy
  • Medicinal Chemistry
  • Protein Kinase C
  • PKC
  • Alzheimer
  • Cancer
  • Affinity Chromatography

Cite this

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title = "Protein Kinase C: synthesis of a C1-domain binding compound as an immobilizable tool for affinity chromatography",
abstract = "Protein kinase C (PKC) belongs to the AGC family of serine/threonine kinases and plays a critical role in the regulation of various aspects of cell functions, including growth, differentiation, metabolism and apoptosis. PKC isoenzymes, as one of the main mediator to convert the extracellular stimuli into biological responses, are activated by phospholipid-derived second messengers and transmit their signal by phosphorylating specific protein substrates. Since protein kinase C is involved in a wide range of signal transduction networks, it represents an interesting and extensively studied molecular target for the treatment of several diseases, such as cancer, and Alzheimer’s disease.Prof. Jari Yli-Kauhaluoma and his team of researchers have been interested in developing simple hydrophobic isophthalic acid derivatives able to modify PKC functions by targeting the C1 domain of the enzyme. A set of small derivatives have been rationally designed and synthesized with a structure-based approach, using the crystal structure of the PKCδ C1B domain. The bis[3-(trifluoromethyl)benzyl] 5-(hydroxymethyl)isophthalate has been selected for further studies due to its high affinity for the C1 domain of PKCα and –δ.The aim of the thesis was to synthesize a new molecule that preserves the scaffold structure of the previous synthesized PKC C1-domain binding compound with a polyethyleneglycol linker attached to it. This new compound will be used as a research tool in affinity chromatography in order to conduct affinity studies and to achieve reliable knowledge on other potential target(s) than PKCs, which could be found in the cell lysate. Furthermore, the future study can provide important clues about the physiological effect of the original ligand on the cell. The work was carried out in the Medicinal Chemistry group of the Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki (Finland).",
keywords = "317 Pharmacy, Medicinal Chemistry, Protein Kinase C, PKC, Alzheimer, Cancer, Affinity Chromatography",
author = "Riccardo Provenzani",
year = "2012",
language = "English",
publisher = "Universit{\`a} degli Studi di Pavia",
address = "Italy",

}

Protein Kinase C: synthesis of a C1-domain binding compound as an immobilizable tool for affinity chromatography. / Provenzani, Riccardo.

Università degli Studi di Pavia, 2012. 90 p.

Research output: ThesisMaster's thesisTheses

TY - THES

T1 - Protein Kinase C: synthesis of a C1-domain binding compound as an immobilizable tool for affinity chromatography

AU - Provenzani, Riccardo

PY - 2012

Y1 - 2012

N2 - Protein kinase C (PKC) belongs to the AGC family of serine/threonine kinases and plays a critical role in the regulation of various aspects of cell functions, including growth, differentiation, metabolism and apoptosis. PKC isoenzymes, as one of the main mediator to convert the extracellular stimuli into biological responses, are activated by phospholipid-derived second messengers and transmit their signal by phosphorylating specific protein substrates. Since protein kinase C is involved in a wide range of signal transduction networks, it represents an interesting and extensively studied molecular target for the treatment of several diseases, such as cancer, and Alzheimer’s disease.Prof. Jari Yli-Kauhaluoma and his team of researchers have been interested in developing simple hydrophobic isophthalic acid derivatives able to modify PKC functions by targeting the C1 domain of the enzyme. A set of small derivatives have been rationally designed and synthesized with a structure-based approach, using the crystal structure of the PKCδ C1B domain. The bis[3-(trifluoromethyl)benzyl] 5-(hydroxymethyl)isophthalate has been selected for further studies due to its high affinity for the C1 domain of PKCα and –δ.The aim of the thesis was to synthesize a new molecule that preserves the scaffold structure of the previous synthesized PKC C1-domain binding compound with a polyethyleneglycol linker attached to it. This new compound will be used as a research tool in affinity chromatography in order to conduct affinity studies and to achieve reliable knowledge on other potential target(s) than PKCs, which could be found in the cell lysate. Furthermore, the future study can provide important clues about the physiological effect of the original ligand on the cell. The work was carried out in the Medicinal Chemistry group of the Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki (Finland).

AB - Protein kinase C (PKC) belongs to the AGC family of serine/threonine kinases and plays a critical role in the regulation of various aspects of cell functions, including growth, differentiation, metabolism and apoptosis. PKC isoenzymes, as one of the main mediator to convert the extracellular stimuli into biological responses, are activated by phospholipid-derived second messengers and transmit their signal by phosphorylating specific protein substrates. Since protein kinase C is involved in a wide range of signal transduction networks, it represents an interesting and extensively studied molecular target for the treatment of several diseases, such as cancer, and Alzheimer’s disease.Prof. Jari Yli-Kauhaluoma and his team of researchers have been interested in developing simple hydrophobic isophthalic acid derivatives able to modify PKC functions by targeting the C1 domain of the enzyme. A set of small derivatives have been rationally designed and synthesized with a structure-based approach, using the crystal structure of the PKCδ C1B domain. The bis[3-(trifluoromethyl)benzyl] 5-(hydroxymethyl)isophthalate has been selected for further studies due to its high affinity for the C1 domain of PKCα and –δ.The aim of the thesis was to synthesize a new molecule that preserves the scaffold structure of the previous synthesized PKC C1-domain binding compound with a polyethyleneglycol linker attached to it. This new compound will be used as a research tool in affinity chromatography in order to conduct affinity studies and to achieve reliable knowledge on other potential target(s) than PKCs, which could be found in the cell lysate. Furthermore, the future study can provide important clues about the physiological effect of the original ligand on the cell. The work was carried out in the Medicinal Chemistry group of the Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki (Finland).

KW - 317 Pharmacy

KW - Medicinal Chemistry

KW - Protein Kinase C

KW - PKC

KW - Alzheimer

KW - Cancer

KW - Affinity Chromatography

M3 - Master's thesis

PB - Università degli Studi di Pavia

ER -