Amino Acids, Peptides and Proteins

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  • Created by: LBCW0502
  • Created on: 13-11-19 15:19
Give examples of therapeutic peptides
Humira, Eliquis, Revlimid, Opdivo, EG-1962, Enbrel, Herceptin, Avastin, Rituxan, Xarelto, Eylea, Remicade, Prevnar 13, Stelara, Lyrica
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State features of the biopharmaceutical pipeline
60% of the pipeline are proteins. Recombinant proteins (20%), vaccines (20%), mAb (40%), antisense (5%), others (20%)
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What is the definition of biopharmaceuticals? (1)
Pharmaceuticals inherently biological in nature due to their method of manufacture, specifically those using biotechnology and involving the use of live organisms. Peptides, proteins, antibodies, nucleic acids, vaccines, gene products
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What is the definition of biopharmaceuticals? (2)
Terms used in pharmaceutical literature - biologics, biopharmaceuticals, products of pharmaceutical biotechnology, biotechnology sourced products, biotechnology medicines
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Outline the structure of insulin
First biopharmaceutical. Hexamer, intrachain disulphide bridge. Ala (in pigs), Thr (in humans). Interchain disulphide bridges
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State features of the hormonal control of erythropoiesis
Stimulus (hypoxia, low blood O2 carrying ability, decreased RBC count, decrease amount of Hb, decreased availability of O2). Kidney releases EPO. EPO stimulates red bone marrow (increase rbc synthesis, carry more oxygen). (Structure)
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What are the levels of protein structure?
Primary, secondary, tertiary, quaternary
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Describe features of water and hydrogen bonding
Weak H bonding, 0.1-0.2 nm H bond in water. Carbonyls, amines and ethers contain H bonds. H bonding between alcohols, carbonyls, peptide bonds, H bonding between DNA (nucleic acid bases)
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What is the hydrophobic effect?
Highly ordered water molecules form cafes around the hydrophobic alkyl chains. H bonds breaking/reforming quickly. Vesicle formation is hydrophobic. Flickering clusters of water molecules in bulk phase
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Describe features of non-polar, aliphatic amino acids
Lack polar functional groups in their side chains. Due to their hydrophobicity of their R groups, often cluster together within interior of proteins, stabilising protein structure via hydrophobic interactions
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Give examples of non-polar, aliphatic amino acids
Glycine, alanine, proline, valine, leucine, isoleucine, methionine – side chains will be on the inside of proteins due to being hydrophobic (e.g. in transmembrane) – C chains
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Describe features of aromatic amino acids
Overall very hydrophobic side chains. R group of tyrosine also contains polar hydroxyl group that can participate in H bonding interactions. R groups of tyrosine and tryptophan absorb UV light at a maximum of 280 wavelength
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Give examples of aromatic amino acids
Phenylalanine, tyrosine, tryptophan – give rise to UV absorbance, also very hydrophobic (found inside protein structures)
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Describe features of polar uncharged amino acids (1)
R groups contain polar functional groups that can H bond with water. Serine and threonine contain hydroxyl groups, asparagine and glutamine contain amide groups and cysteine contains a sulfhydryl group
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Describe features of polar uncharged amino acids (2)
Sulfhydryl group of cystine side chain is a weak acid (pKa of 8.2). Cysteine side chain is mostly uncharged at neutral pH
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Give examples of polar uncharged amino acids
Serine, threonine, cysteine, asparagine, glutamine (alcohol or amide groups) – can H bond, found on the outside of the protein structure, not found in the membrane
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Describe features of cysteine and disulphide bonds (1)
Thiol groups of two cysteine residues are readily oxidised to form a covalently linked dimeric amino acid known as cystine. In cystine, two residues are joined by a disulfide bond. Disulfide linked cystine residue is strongly hydrophobic
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Describe features of cysteine and disulphide bonds (2)
In proteins, disulfide bonds form covalent links between different parts of a polypeptide chain or between two different polypeptide chains
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Describe features of cysteine and disulphide bonds (3)
Hydrophobic (due to SH loss, pKa of 8, lost when disulphide bond formed, SH not on its own due to being reactive). Curly hair, straight hair
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Describe features of positively charged amino acids
Side chains fully positively charged at neutral pH
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Give examples of positively charged amino acids
Lysine (primary amino group attached to e carbon of side chain). Arginine (guanidinium group of side chain is positively charged). Histidine (R group contains an aromatic imidazole group that is particularly positively charged at neutral pH)
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Describe features of negatively charged amino acids (and give examples) - 1
R groups of aspartate and glutamate contain carboxyl groups that are fully negatively charged at neutral pH (pKas of 3.65 and 4.25). Aspartate (carboxyl group is attached to the beta carbon of the amino acid backbone)
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Describe features of negatively charged amino acids (and give examples) - 2
Glutamate (carboxyl group attached to gamma carbon)
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Describe features of amino acid modification
Add phosphate group to amino acids (e.g. phosphoserine, phosphothreonine, phosphotyrosine). Other modified amino acids - N-methylarginine, N-acetyllysine, glutamate methyl ester, adenylyltyorsine. Post translational modification (protein-ligand))
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Describe features of charged amino acids
Zwitterionic form predominates at neutral pH. Non-ionic form doesn't occur in significant amounts in aqueous solution at any pH. Zwitterion can act as either an acid (proton donor) or base (proton acceptor)
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What is the isoelectric point?
The pH at which the positive equals the negative charge (no net charge). Varies based on side chain in amino acid. pI = pKa 1 + pKa 2 /2. Amino acid least soluble in water and amino acid doesn't migrate in electric field (electrophoresis, electrodes)
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Describe features of peptide bonds (1)
Condensation reaction. Amino group of one amino acid acts as nucleophile to displace hydroxyl group of another amino acid to form peptide bond. Amino groups are good nucleophiles, OH is a poor leaving group (not readily displaced)
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Describe features of peptide bonds (2)
At physiological pH, reaction doesn't occur to any appreciable event. Peptide bonds are generated via a dehydration synthesis reaction. Amide bond (pi-pi, N-terminus to C-terminus)
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Give examples of peptide hormones
Bradykinin (inhibits inflammation of tissue). Vasopressin (regulates body retention of water, release in response to stress). Oxytocin (induces labour and stimulates milk production). Leucine enkephalin, methionine enkephalin (pain). Aspartame
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Describe features of peptide bond resonance (1)
Lone pair of electrons on N is delocalised onto carbonyl oxygen. N is not basic, carbonyl is not reactive. N-C=O is planar. Rotation around peptide bond not permitted. Rotation around bonds connected to alpha C is permitted. Phi (amide N bond)
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Describe features of peptide bond resonance (2)
Psi (carbonyl C bond). Both angles are 180 degrees
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Describe features of the planar peptide group (1)
Three bonds separate sequential alpha carbons in polypeptide chain. N-C and C-C bonds can rotate, dihedral angles (phi/psi). Peptide C-N bond not free to rotate
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Describe features of the planar peptide group (2)
Other single bonds in backbone may be rotationally hindered depending on size and charge of R groups
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Which type of plot can be used to determine levels of a protein structure?
Ramachandran plot (able to determine ideal angles for structures)
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What are the four main interactions within a protein structure?
Electrostatic forces, H bonds, van der Waals, hydrophobic forces
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What is the main interaction in an alpha helix?
H bond between residues i and i+4 (small hydrophobic residues such as Ala and Leu are strong helix formers)
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Which amino acids act as helix breakers?
Pro acts as a helix breaker due to N-C bond rotation being impossible. Gly acts as a helix breaker because the tiny R group supports other conformations
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What are the two types of beta pleated sheets?
Anti-parallel (structures in opposite directions, symmetrical). Parallel (structures in the same direction, at angles). Can get mixed beta pleated sheet
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Describe features of turns (1)
Beta turns occur when strands of beta sheets change direction. 180 degrees turn achieved over 4 amino acids. Turn stabilised by H bond from a carbonyl oxygen to amide proton three residues down the sequence
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Describe features of turns (2)
Proline in position 2 or glycine in position 3 are more common in beta turns
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Describe features of steric hindrance
While many angles of rotation are possible, only a few are energetically favourable. Trans (stable), cis (interaction)
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Describe features of proline cis-trans
Structures of beta turns. Isomers involves imino N of proline. Mainly in trans configuration. Very few in cis configuration (can occur at beta turns)
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What are the Chou-Fasman parameters?
Determines which amino acids were found in different protein structures e.g. alpha helix, beta pleated sheet, turns
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