Chemistry 106: Drugs in Society Lecture 17: Where Do Macromolecular Targets Come From? 5/07/18

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1 Chemistry 106: Drugs in Society Lecture 17: Where Do Macromolecular Targets Come From? 5/07/18 By the end of this session, you should be able to 1. Know the general scheme of tissue organization, from molecules to man; i.e., atoms molecules, molecules organelles, organelles cells, cells tissues, tissues organs, organs organ systems, organ systems organisms 2. Appreciate that every cell contains all the information necessary to produce a complete individual, and marvel at the body s ability to turn various functions of cells on and off in order to generate a functional person 3. Know the basic structure of the animal cell, in particular the relationship of the nucleus and DNA with the rough (ribosome containing) endoplasmic reticulum 4. Know the structure of the cellular membrane, in particular the need to embed proteins within it for cellular communication 5. Know amino acids make up proteins 6. Know the general roles proteins play in the function of the cell and as such, the function of the body. Major examples includes nucleic acid binding proteins, signal transduction [communication] proteins, and enzymes 7. Know what the primary structure of a protein is, and how the primary structure gives rise to the overall 3 dimensional structure 8. Know the 3 dimensional structure of DNA is driven by histone proteins which act to spool DNA 9. Know DNA needs to be unspooled to be copied, and histone proteins can be modified [acetylated] to make this happen 10. Know that cytosine pairs with guanine (CG) and adenine pairs with thymine (AT) in DNA replication, allowing information to be copied 11. Know the basic components involved with the replication of DNA, and why it must occur for a species to survive 12. Know the basic process leading from transcription to translation. Be able to define gene, promoter region, TATA box, messenger RNA (mrna), introns, exons, codons, transfer RNA (trna), and ribosomes 1

2 From Atom to Adam 2

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4 Amino Acids and Proteins Proteins not only provide cellular structure, they also do the work of the cell, including how and when the information contained in DNA is expressed the ultimate chicken and egg question since expression of DNA ultimately leads to proteins needed to carry out a particular function. General Use of Proteins Proteins are Composed of Amino Acids Linked Together 4

5 The Sequence of Amino Acids (Primary Structure) Gives Rise to 3 Dimensional Structure and Ultimately Function The question then becomes How are proteins made so they can carry out their function? That is, what tells the cell to build specific proteins at specific times to carry out the various functions required for survival? 5

6 Structure of DNA 6

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8 Replication Clearly, if information is going to be carried forward from generation to generation, DNA must be able to replicate 8

9 In order to replicate, the DNA must unwind to expose the double-stranded DNA. This is done by the acetylation of histone proteins. Histone proteins have lots of positive charge on them and acetylation removes that charge. DNA has lots of negative charge, and when the plus-minus interaction is lost the DNA unspools. When replication is complete, the acetylation is reversed, leading to the compaction of DNA Rapidly dividing cells leave the DNA unspooled much more of the time. Since cancer cells tend to divide rapidly, this affords some selectivity between cancer cells and normal cells, since most normal cells are not actively dividing on a routine basis. Selectivity is the key to developing drugs and this crude selectivity is the principal means by which cancer chemotherapeutic drugs work Some Intercalating Cancer Chemotherapeutic Agents: Idamycin Adriamycin Cerubidine 9

10 We have seen that replication allows a new copy of a cell to be made. It is transcription and translation that makes the proteins within a cell that allows its structure and function Transcription mrna Processing The key points here are Genes encode for proteins DNA must be unraveled and separated so the message/instructions for a particular amino acid sequence can be copied (the m in mrna stands for messenger) 10

11 The gene contains 2 regions o The promoter region which is not copied, but instead controls the making of the mrna (remember, no mrna, no protein) by allowing or preventing RNA polymerase from binding Translation o The structural portion which contains the 3 base sequence which calls for a given amino acid we call these 3 base sequences codons Occurs in the protein factories, the ribosome Since the ribosome is outside of the nucleus, the mrna needs to be shipped to the factory The 3 base codon on the mrna calls for a trna (transfer ribonucleic acid) containing a specific amino acid. In this way, the trna acts as a molecular translator converting mrna into protein By bringing 2 trna s loaded with amino acids together, the amino acids may be tied together. As the trna s lose their amino acid attachment, they fall off the ribosome as the ribosome moves down the mrna, as shown below 11

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