Introduction to Medicinal Chemistry - Drug Targets Proteins PDF

# An Introduction to Medicinal Chemistry ## Chapter 3: Drug targets proteins **Salih Al-Jabour, Dr.rar.nat** **Pharmacy Department** **AlQuds University** **Jerusalem, Palestine** ## 1. The building blocks for proteins - Proteins are macromolecules made up of amino acid building blocks - The...

# An Introduction to Medicinal Chemistry ## Chapter 3: Drug targets proteins **Salih Al-Jabour, Dr.rar.nat** **Pharmacy Department** **AlQuds University** **Jerusalem, Palestine** ## 1. The building blocks for proteins - Proteins are macromolecules made up of amino acid building blocks - There are 20 common amino acids in human proteins ## 2. Zwitterions Zwitterions: formerly called a dipolar ion, is a molecule with two or more functional group, of which at least one has a positive and one has a negative electrical charge and the net charge of the entire molecule is zero ## 3. Amino Acids ### Non-zwitterions - Non-ionized form of amino acids ### Zwitterions - Ionized form of amino acids (zwitterion) - Amino acids are chiral molecules (except glycine, R=H) ### Chirality and the R, S system - H<C<N<O - R-clockwise - S-counterclockwise ### Mirror image - non-superimposable mirror images ### Enantiomers - isomers L (R), D (S) - Each amino acid has an identical head group. - Only L-amino acids are present in human biochemistry - The L-amino acids are R-enantiomers. (except cysteine; R = CH2SH) ## 4. Codes for amino acids | NAME | 3 LETTER CODE | ONE LETTER CODE | |:---------------|:----------------:|:----------------:| | Alanine | Ala | A | | Arginine | Arg | R | | Asparagine | Asn | N | | Aspartic acid | Asp | D | | Cysteine | Cys | C | | Glutamic acid | Glu | E | | Glutamine | Gln | Q | | Glycine | Gly | G | | Proline | Pro | P | | Serine | Ser | S | | Tyrosine | Tyr | Y | | Histidine | His | H | | Isoleucine | Ile | I | | Leucine | Leu | L | | Lysine | Lys | K | | Methionine | Met | M | | Phenylalanine | Phe | F | | Threonine | Thr | T | | Tryptophan | Trp | W | | Valine | Val | V | ## 5. A Guide to the Twenty Common Amino Acids ### Chart Key: - **Aliphatic**: **Alanine**, **Glycine**, **Isoleucine**, **Leucine**, **Proline**, **Valine** - **Aromatic**: **Phenylalanine**, **Tryptophan**, **Tyrosine** - **Acidic**: **Aspartic Acid**, **Glutamic Acid** - **Basic**: **Arginine**, **Histidine**, **Lysine** - **Hydroxylic**: **Serine**, **Threonine**, **Tyrosine** - **Sulfur-containing**: **Cysteine**, **Methionine** - **Amidic**: **Asparagine**, **Glutamine** - **Non-Essential**: **Alanine**, **Asparagine**, **Aspartic Acid**, **Cysteine**, **Glutamine**, **Glutamic Acid**, **Glycine**, **Proline**, **Serine**, **Tyrosine** - **Essential**: **Arginine**, **Histidine**, **Isoleucine**, **Leucine**, **Lysine**, **Methionine**, **Phenylalanine**, **Threonine**, **Tryptophan**, **Valine** ## 6. Willie Taylor's Scheme ### Hydrophobic - Glycine - Alanine - Proline - Leucine - Tryptophan - Valine - Phenylalanine - Isoleucine - Methionine ### Polar - Serine - Cysteine - Threonine - Tyrosine ### Charged (-) - Glutamine - Asparagine - Glutamic Acid - Aspartic Acid ### Charged (+) - Histidine - Lysine - Arginine ## 7. A summary of the metabolic pathways of amino acids - **Ketogenic**: **Tryptophan**, **Tyrosine**, **Phenylalanine**, **Threonine**, **Isoleucine**, **Lysine**, **Leucine** - **Glucogenic**: **Alanine**, **Glycine**, **Cysteine**, **Serine**, **Threonine**, **Tryptophan** - **Both Glucogenic and Ketogenic**: **Arginine**, **Proline**, **Histidine**, **Glutamine**, **Methionine**, **Isoleucine**, **Valine** ## 8. The primary structure of protein - Amino acids are linked by **peptide bonds** - **Dipeptide**: two amino acids linked together ## 9. The secondary structure of protein - **Φ**, **ψ** (phi and psi torsion angles) - **α-helix**: right-hand alpha helix, left-hand alpha helix (rare) - **β-sheet**: antiparallel beta sheet, parallel beta sheet - **3D Ramachadron plot**: ## 10. The tertiary structure of proteins - **Overall shape of the protein** - Maximises favourable interactions and minimises repulsive interactions - **Types of Interactions**: - **Ionic Bonding Interactions**: The interaction between oppositely charged ions - **Hydrogen Bonding Interactions**: The interaction between a hydrogen atom, covalently linked to a highly electronegative atom, such as oxygen or nitrogen, and another electronegative atom. - **Van der Waals interactions**: attractive or repulsive forces between molecules - **Covalent bonds**: Disulfide links - **Ionic or electrostatic bonds (salt bridges)** - **Hydrogen bonds**: are a type of dipole-dipole interaction between a lone pair on a highly electronegative atom (such as oxygen or nitrogen) and a hydrogen covalently linked to an electronegative atom. <start_of_image> Schematic diagram for the folding of a protein, showing a protein folding into a compact structure with a hydrophobic core and a hydrophilic surface. ## 11. The quaternary structure of proteins - Arrangement of protein subunits with respect to each other ## 12. Protein function - **Structural proteins**: tubulin - **Transport proteins**: Transport polar molecules across the hydrophobic cell membrane. Polar molecules transported include amino acids and neurotransmitters. # Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformation changes of Fur - **Salih Jabour**, **Mazen Y. Hamed** - **Received**: 9 July 2008, **Accepted**: 3 November 2008, **Published online**: 21 November 2008 - **Springer Science+Business Media B.V. 2008** The attachment has been converted into a structured markdown format. The images are not included but are described. The document is a powerpoint presentation discussing the structure and function of proteins. There are many diagrams depicting this information.