Amino Acids, Peptides and Proteins.ppt

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1、Amino Acids, Peptides and Proteins,Convener : Dr. Fawaz Aldabbagh,Third Year Organic Chemistry,CO-303 Natural Product Chemistry,Primary, Secondary, Tertiary and Quaternary structures of Proteins. Isoelectric Point. Prosthetic Group. Investigation of amino acid structure of a protein. Peptide Synthes

2、is,Amino Acids,All DNA encoded aa are ,All are chiral, except Glycine R = H,All DNA encoded aa are usually L-,Of the 20 aa, only proline is not a primary aa,aa are high melting point solids! Why?,Answer = aa are ionic compounds under normal conditions,Isoelectric Point = concentration of zwitterion

3、is at a maximum and the concentration of cations and anions is equal,For aa with basic R-groups, we require higher pHs, and for aa with acidic R-groups, we require lower pHs to reach the Isoelectric Point,Isoelectric Point is the pH at which an aa or peptide carries no net charge.i.e. RCOO- = RNH3+S

4、o, for basic R-groups, we require higher pHs, and for acidic R-groups we require lower pHs,e.g. Isoelectric point for gly pH = 6.0Asp pH = 3.0Lys pH = 9.8Arg pH = 10.8,Preparation of Amino Acids,The Strecker Reaction,Preparation of Optically active Amino Acids - (Asymmetric Synthesis),Prepare the ta

5、rget aa in racemic form, and separate the enantiomers afterwards,Resolution,1. Crystallisation with a chiral Counter-ion,Strechnine,2. Form Diastereotopic Peptides 3. Chiral HPLC 4. Enzyme Resolution,Form the N-ethanoyl (acetyl) protected aa then treat with an acylase enzyme.,Test for Amino Acids -

6、Ninhydrin,aa are covalently linked by amide bonds (Peptide Bonds) The resulting molecules are called Peptides & Proteins,Features of a Peptide Bond; Usually inert Planar to allow delocalisation Restricted Rotation about the amide bond Rotation of Groups (R and R) attached to the amide bond is relati

7、vely free,aa that are part of a peptide or protein are referred to as residues.,Peptides are made up of about 50 residues, and do not possess a well-defined 3D-structureProteins are larger molecules that usually contain at least 50 residues, and sometimes 1000. The most important feature of proteins

8、 is that they possess well-defined 3D-structure.,Primary Structure is the order (or sequence) of amino acid residues,Peptides are always written and named with the amino terminus on the left and the carboxy terminus on the right,Strong Acid Required to hydrolyse peptide bonds,Cysteine residues creat

9、e Disulfide Bridges between chains,This does not reveal Primary Structure,Dr. Frederick Sanger, Nobel Prize for Chemistry 1958 and 1980 Peptide sequencing,Prof. R. B. Merrifield Nobel Prize for Chemistry 1984 Automated Peptide Synthesis,Prof. Linus Pauling,Secondary Structure,The Development of Regu

10、lar patterns of Hydrogen Bonding, which result in distinct folding patterns,-helix,-pleated sheets,Tertiary Structure,This is the 3D structure resulting from further regular folding of the polypeptide chains using H-bonding, Van der Waals, disulfide bonds and electrostatic forces Often detected by X

11、-ray crystallographic methods,Globular Proteins “Spherical Shape” , include Insulin, Hemoglobin, Enzymes, Antibodies -polar hydrophilic groups are aimed outwards towards water, whereas non-polar “greasy” hydrophobic hydrocarbon portions cluster inside the molecule, so protecting them from the hostil

12、e aqueous environment - Soluble Proteins,Fibrous Proteins “Long thin fibres” , include Hair, wool, skin, nails less folded - e.g. keratin - the -helix strands are wound into a “superhelix”. The superhelix makes one complete turn for each 35 turns of the -helix.,In globular proteins this tertiary str

13、ucture or macromolecular shape determines biological properties,Bays or pockets in proteins are called Active Sites Enzymes are Stereospecific and possess Geometric Specificity,Emil Fischer formulated the lock-and-key mechanism for enzymes,The range of compounds that an enzyme excepts varies from a

14、particular functional group to a specific compound,All reactions which occur in living cells are mediated by enzymes and are catalysed by 106-108,Some enzymes may require the presence of a Cofactor. This may be a metal atom, which is essential for its redox activity. Others may require the presence

15、of an organic molecule, such as NAD+, called a Coenzyme. If the Cofactor is permanently bound to the enzyme, it is called a Prosthetic Group.,For a protein composed of a single polypeptide molecule, tertiary structure is the highest level of structure that is attained,Myoglobin and hemoglobin were t

16、he first proteins to be successfully subjected to completely successful X-rays analysis by J. C. Kendrew and Max Perutz (Nobel Prize for Chemistry 1962),Quaternary Structure,When multiple sub-units are held together in aggregates by Van der Waals and electrostatic forces (not covalent bonds) Hemoglo

17、bin is tetrameric myglobin,For example, Hemoglobin has four heme units, the protein globin surrounds the heme Takes the shape of a giant tetrahedron Two identical and globins. The and chains are very similar but distinguishable in both primary structure and folding,Peptide Synthesis,Three Criteria for a Good Protecting Group?,What is the best way to activate the Carboxyl group?,Protecting Groups,Protecting NH2,Protecting COO-,