Production of Modified Megestrol by Jittima Khorungkul.

Slides:

Advertisements

Similar presentations

Novel Drug Marketing Group 2 Mahinda C. Edirisooriya.

Advertisements

1 Mechanism Testing of the Drug (Modified Megestrol) Mr.Pasavi Ratchapongsirikul.

20,000 GENES IN HUMAN GENOME; WHAT WOULD HAPPEN IF ALL THESE GENES WERE EXPRESSED IN EVERY CELL IN YOUR BODY? WHAT WOULD HAPPEN IF THEY WERE EXPRESSED.

Novel Drug Design Modified Megestrol by Group II.

2 nd lecture: Communications among cells and tissues Classification of hormones in Several Ways: According to solubility According to chemical composition.

Cell Communication II Chapter 15. An animal cell depends on extracellular signals to survive or divide.

1 The Chemistry of Life Mark Mayo Cypress College Last update 9/10/13.

Thurs review Signal transduction mechanisms –Gated ion channels Neuronal signaling, muscle contraction nACh receptors, Na + channels, K + channels, Ca.

Step 1 of Protein Synthesis

2.7 DNA Replication, transcription and translation

Molecular Physiology: Enzymes and Cell Signaling.

DNA Replication…Notes Steps: 1.A section of the DNA molecule unwinds and becomes a ___________________ladder. 2.The 2 nucleotide chains are separated by.

DNA Structure DNA consists of two molecules that are arranged into a ladder-like structure called a Double Helix. A molecule of DNA is made up of millions.

AP Biology Control of Eukaryotic Genes.

Chemical Basis of Life. Ionic Bonding

What are proteins? Enzymes,antibodies,many hormones,and substances that help the blood to clot,are all proteins. Enzymes,antibodies,many hormones,and.

Transcription DNA  mRNA. Review What was the purpose for DNA replication? What was the purpose for DNA replication? So cell division (mitosis & meiosis)

RNA and PROTEIN SYNTHESIS Chapter 13-1 & 13-2

Design and Production of a GFP and Human IL-13 Linked Chimeric Protein in E. coli Using pQE-30 Vector Stephen R. Suknaic Department of Biology, York College.

Response: Cell signaling leads to regulation of transcription or cytoplasmic activities Chapter 11.4.

From Gene To Protein Chapter 17. From Gene to Protein The “Central Dogma of Molecular Biology” is DNA  RNA  protein Meaning that our DNA codes our RNA.

Cytokines, Growth Factors and Hormones SIGMA-ALDRICH.

Do Now: 1) How do somatic and sex cell mutations differ. 2) A mutation causes the adenine in the following sequence to be changed to a guanine. How does.

AP Biology DNA Study Guide. Chapter 16 Molecular Basis of Heredity The structure of DNA The major steps to replication The difference between replication,

Michael Cummings David Reisman University of South Carolina Gene Regulation Part 2 Chapter 9.

Trp Operon A brief description. Introduction a repressible system In this system, though, unlike the lac operon, the gene for the repressor is not adjacent.

Gene Expression. Cell Differentiation Cell types are different because genes are expressed differently in them. Causes:  Changes in chromatin structure.

Ch. 17 From Gene to Protein. Genes specify proteins via transcription and translation DNA controls metabolism by directing cells to make specific enzymes.

Transcription and mRNA Modification

Transcription DNA  mRNA. Objectives Explain the purpose of transcription for a cell Explain the purpose of transcription for a cell Tell how RNA differs.

Biochemistry Sixth Edition Chapter 31 The Control of Gene Expression Part II: Eukaryotes (cis vs. trans) Copyright © 2007 by W. H. Freeman and Company.

Protein Synthesis: Protein Synthesis: Translation and Transcription EQ: What is the Central Dogma and what processes does it involve? Describe processes.

MACROMOLECULES. The four macromolecules are: Carbohydrates Proteins Lipids Nucleic acids.

Functions of RNA mRNA (messenger)- instructions protein

Protein Synthesis The process of protein synthesis is explained by the central dogma of molecular biology, which states that: DNA  RNA  Proteins How.

Protein Synthesis “From code into Flesh & Blood”.

DNA and Protein Synthesis Ch. 12 and 13. Youtube Review

1 From Bi 150 Lecture 0 October 4, 2012 An introduction to molecular biology... but you will learn the cell biology in this course.

From Gene to Protein Transcription and Translation.

How is gene expression in eukaryotes accomplished ?

Protein Synthesis Introduction Chapter 17. What you need to know! Key terms: gene expressions, transcription, and translation How eukaryotic cells modify.

Protein Synthesis Who am I? How was I formed? Where’s my mom? A molecular model of the YiiP zinc transporter protein with bound zinc ions (red spheres).

RNA & Protein Synthesis

PROTEINS. LIFE IS AN ORGANIZED SYSTEM OF COMPLEX CHEMICAL REACTIONS.

Click to continue How do a few genes build a diversity of body parts? There’s more in the genetic toolkit than just genes! Click your forward cursor to.

Regulation of gene expression Fall, Gene Expression Regulation in Prokaryotes it includes : Control of transcription, little on translation How.

Alignment table: group 4

Control of Gene Expression

Gene Expression.

Proteolysis Targeting Chimera Profacgen. In mammalian cells, protein degradation is mainly carried out by the ubiquitin- proteasome system to dispose.

Gunjan Desai Emily Grupe Allison Heschle Adam Vanore

Ribosomes and Protein Synthesis (Ch 13.2)

Endocrine System Chemical Control.

Gene Expression 1. Gene expression is the activation of a gene that results in transcription and the production of mRNA. Only a fraction of any cell’s.

Molecular Genetics Are we controlled by our DNA?

Cell Signaling.

RNA: The other nucleic acid

DNA and Protein Synthesis

Chapter 17 From Gene to Protein.

Analogy Video Central Dogma Analogy Video (Resources Page)

Unit III Information Essential to Life Processes

General Animal Biology

Comparison of Nuclear, Eukaryotic RNA Polymerases

Macromolecules Biology ch. 2-3.

Organic Chemistry and the Importance of Carbon

Dr. Israa ayoub alwan Lec -7-

Chapter 17 From Gene to Protein.

Volume 12, Issue 7, Pages (July 2005)

Presentation transcript:

Production of Modified Megestrol by Jittima Khorungkul

Modified Megestrol Production Goal: Synthesis bifunctional molecule that can use in Liver cancer treatment Bifucntional molecule:  Produce DNA adduct  Specific binding the estrogen receptor with high affinity

Megestrol Estrogen receptor DNA adduct Binding to vER Bifunctional molecule structure Ligand Domain Linker War Head

Expression of essential gene Undamaged cell Nuclear protein (e.g.ER) promoter How modified megestrol work….. Estrogen and ER complex

Adduct shielded from Repair DNA repair enzyme Adduct persists

Adduct shielded from Repair In non-cancer cell (less express of vER) DNA repair enzyme adduct

Adduct shielded from Repair Cancer cell (over express of vER)

Adduct “Hijacks” Transcription Factor X Cancer cell (over express of vER)

Modified megestrol N,N -bis-chloroethylaniline (War Head) Alkyl-amino-carbamate (Linker) Megestrol acetate (Ligand Domain) Consisted of : (CH 2 ) 6 -N-(CH 2 ) 2 -0 N-(CH 2 ) 3 - -N H O H (CH 2 ) 2 C l Ligand DomainLinker War Head

Modified megestrol Megestrol acetate (Ligand Domain) -Binding to the linker at 7 alpha position  Large alkyl groups can be attached with retention of high affinity for ER Megestrol acetate 7 alpha position

Modified megestrol N,N -bis-chloroethylaniline (War Head) - Ability to alkylate DNA - From covalent DNA adduct at the N7 position of guanines

Modified megestrol Alkyl-amino-carbamate (Linker) Consist of - amino - carbarmate group  provide a relatively rigid connection  resistant to hydrolytic enzyme

Synthesis Procedure (1) (2) (3) (4)(5)

Synthesis Procedure

Final Product: Modified megestrol

Properties of Modified Megestrol Chemical Formula: C 42 H 65 Cl 2 N 3 O 4 Exact Mass: Molecular weight: Element Analysis: C, 67.54; H, 8.77; Cl, 9.49; N, 5.63; O, 8.57

Summary Modified Megestrol -Modified Megestrol is the bifunctional molecule that consist of ‘Warhead’, ‘Linker’ and ‘Ligand binding domain’ -It has the abilities to produce DNA adduct and capable of binding the vER - vER-DNA adduct complexes will shielded from DNA repair enzyme War head Linker Megestrol acetate