Chapter 1 • What is Chemical Biology Using chemistry tools to advance the molecular understanding of biology at the level of atoms and bonds. Using biology tools to advance chemistry. Genome: genome is a collection of all genes in an organism. Genotype: the genetic constitution of an individual organism Phenotype: physical outcomes of genes Different transcription levels control phenotypes Transcriptome: The collection of all RNA transcripts in a cell, tissue, or organism. RNA splicing (removal of the inserts) amplifies the diversity of the genome. Proteome: Proteome is the collection of all proteins in a cell, tissue, or organism. • Evolution applications on chemical biology. Generate diversity Bio-oligomers Combinatorial shuffling ‒ Select for fittest Criteria for fittest ‒ Used extensively • Tools in chemical biology: colorimetric indicators: Chromophores and Fluorophores, can provide a useful indicator for the presence of a particular molecule • For example: Fluorophores absorb photon of light, and emit a photon at a higher wavelength lower energy • Can select for just the lower wavelength with a filter to see only the molecule of interest • Extremely sensitive (down to single molecule under the right conditions) Use absorbance for quantitative analysis • Often rely on antibodies to specifically bind to a particular molecule This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ • If the antibody is attached to an enzyme, can see presence of the molecule as turnover of a dye , microbiological screens, Darwinian evolution in action • Select for life/death or color or other identical phenotypes Very efficient at infecting cells • Ruthlessly amplify copies of themselves • Provides a powerful tool for selections phage display.: Powerful technique to identify protein with specific abilities. • Such as the ability to bind with affinity to a target molecule To identify binding partners • Binder selected from library of 5 x 10 15 different RNA sequences Combinatorial synthesis: Modular architecture allows combinatorial synthesis. Easy to mix and match components, as all connected in the same way. Antibodies are proteins bind to antigens : Professional binding proteins. One of the immune system’s first lines of defense. Chapter 2 • Electrophiles and Nucleophiles, arrow pushing. Nucleophile: Electron-rich species that donate electron pairs to electrophile in a polar bond-forming reaction, Is a Lewis base • Electrophile: Substances that accept electron pairs from a nucleophile, Is a Lewis acid Electrons move from a nucleophilic source to an electrophilic sink The nucleophilic site can be neutral or negatively charged The electrophilic site can be neutral or positively charged The octet rule should be followed This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ Arrow pushing rule: Arrows never indicate the motion of atoms Arrows never start or end on charge Arrows begin with lone pairs, pi bonds or sigma bonds, and end on un-filled orbitals In molecular orbital theory, Arrows depict the interaction of filled and un-filled orbitals. • Identify HOMO and LUMO: highest occupied molecular orbital and lowest unoccupied molecular orbital • Common reactions related to amines, carbonyl compounds, and phosphoric acids. Electronegativity differences cause polar bonds, nucleophilic sites and electrophilic sites in a molecular • Arrow pushing: From nucleophile to electrophile From HOMO to LUMO • Basicity of amines comes from the lone pair, nucleophile • Carbonyl compounds: nucleophilic O, electrophilic C, can stabilize a negative charge • Phosphate is similar to carbonyl compounds in terms of reactivity. • Formose reaction: This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ • Hydrogen bond donors and acceptors. Largely a coulombic interaction • Very sensitive to environment and geometry • Between 3 atoms: a donor atom (highly EN), an acceptor atom with lone pair electrons, and a proton • Strong when involve highly electronegative donor and acceptor atoms such as oxygen and nitrogen. • Calculate coulombic potential and Lennard-Jones potential changes. This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ Chapter 3 • Be able to draw simple DNA structures. The double helix structure of DNA, all DNA are right-handed. Double helix come from the minor groove and major groove The connectivity (phosphodiester bond), the importance of lacking the 2-OH The direction of DNA sequence: 5’-3’ Bases are not that basic DNA bases can be modified, commonly methylated Watson-Crick base pairs (AT and GC) from U-shape • DNA structures and forces in DNA, Watson-Crick base pairing. Forces hold double strand DNA: H-bonding and Pi-stacking • GC, CG, AT, TA base pairs give different H-bonding donor/acceptor patterns in both major groove and minor groove, were transcription factors will decode. • Intercalators. Sliding into the DNA pi-stacking Flat, aromatic and positively charged Examples of DNA intercalations: planer, aromatic, positive charged • Wallace rule. Watson-Crick base pairs form U-shape and Stacking U-shaped blocks results in major and minor groove • DNA superstructures and protein modifications. This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ would into supercoils DNA is inherently coiled into double helix Then forms additional coiling Bacterial plasmids. • The mechanism of beta-lactam antibiotics. • Biosynthesis of DNA and PCR Biosynthesis of DNA: DNA polymerase extend an existing strand by adding 5’ nucleotide triphosphate to the 3’ end of the growing strand Only RNA polymerase can start from scratch DNA polymerase has two Mg2+ ions. Reverse transcriptase: polymerizes DNA from RNA template Common mechanism with Taq DNA polymerase (PCR) Right-hand mechanism DNA Polymerase and Reverse transcriptase Only works in 5’ to 3’ direction This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ • If double stranded DNA is 1 m in diameter... DNA polymerase: Dream machine 1 m • DNA microarray. Each spot has a different oligonucleotide: each oligonucleotide hybridizes to a different mRNA transcript. DNA microarrays monitor transcription of thousands of gens simultaneously 26 mm 75 mm • DNA sequencing. Incorporation of very low percentage of dideoxy terminators makes a bunch of short DNA fragments Separate fragments by capillary electrophoresis Human genome contains about 3 billion of these base pairs in 23 pairs of chromosomes • Based on first generation sequencing • High-throughput • Sequence human genome in 1 hou • DNA technologies include cutting, pasting, and mutagenesis. Cutting and pasting of DNA are used extensively in Biotech Programs cells to synthesize specific DNA sequence Used to encode instructions for biosynthesis by cells and organisms Symmetry sets up recognition of a symmetric sequence Restriction enzymes and DNA ligase Can put together arbitrary sequences of DNA T4 DNA ligase, slow, overnight incubation •DNA reactivity, big nucleophile, alkylating reagents: N-nitrosoamines This study source was downloaded by 100000786664641 from CourseHero.com on 04-22-2024 02:13:03 GMT -05:00 https://www.coursehero.com/file/215118998/Exam1-CHEM4240docx/ Powered by TCPDF (www.tcpdf.org)
