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UVM CHEM 205 - Amino Acids and Polypeptides

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Lectures 4-5 Amino Acids and PolypeptidesAmino Acids: Building Blocks of ProteinsAmino Acids can Polymerize via Peptide Bonds• All but glycine are chiral• (R,S)-nomenclature system is superior - amino acids like isoleucine andthreonine (two chiral centers) can be named unambiguously• However older D,L-nomenclature prevails• D,L-nomenclature is based on D- and L-glyceraldehyde• L-amino acids predominate in nature• Most amino acids are (S) (except for cysteine)Stereochemistry of Amino AcidsWhy is this such a big deal?D,L (Fischer) Nomenclature• Horizontal substituents are pointing towards you• Vertical substituents are pointing away• Carbon in highest oxidation state is at the top• D if the non-hydrogen group is to the right• For glycine both horizontal groups are H - achiral• For isoleucine and threonine (2 chiral centers)• D and L are defined by the position of the amino group• Non-natural chirality at the b-carbon is indicated by the prefix allo- and is rather ambiguousD,L (Fischer) Nomenclature (continued)(R,S) (Cahn Ingold Prelog) Nomenclature20 Common Amino AcidsYou should know names, structures, pKa values, 3-letter and 1-letter codes• Non-polar amino acids• Polar, uncharged amino acids• Acidic amino acids• Basic amino acidsNon-Polar (Hydrophobic) Amino AcidsPolar Uncharged Amino AcidsCharged Basic Amino AcidsCharged Acidic Amino AcidsUncommon Amino Acids• Hydroxylysine, hydroxyproline - collagen• Carboxyglutamate - blood-clotting proteins• Pyroglutamate - bacteriorhodopsin• Phosphorylated amino acids - cellular signaling• Majority are post-translationally modifiedWe'll see some of these in later chaptersAcid-Base ChemistryH2A+ + H2O Æ HA + H3O+ Ka1 = [ HA] [ H3O+ ] [H2A+ ]eg for glycine:H3N+-CH2-CO2H + H2O Æ H3N+-CH2-CO2¯ + H3O+Amino acids are weak polyprotic acidsHA + H2O Æ A¯ + H3O+ Ka2 = [ A¯ ] [ H3O+ ] [ HA ]eg for glycine:H3N+-CH2-CO2¯ + H2O Æ H2N-CH2-CO2¯ + H3O+The second dissociationpKa Values of the Amino AcidsYou should know these numbers and know what they mean!• Alpha carboxyl group - pKa = 2• Alpha amino group - pKa = 9• These numbers are approximate, but they’re close enoughfor most purposespKa of Amino Acid Side-Chains• Arginine, pKa(guanidino group) 12.5• Aspartate, pKa (carboxylate) 3.9• Cysteine, pKa (thiol) 8.3• Glutamate, pKa (carboxylate) 4.3• Histidine, pKa (imidazole) 6.0• Lysine, pKa (amine) 10.5• Serine, pKa (alcohol) 13• Threonine, pKa (alcohol) 13• Tyrosine, pKa (phenol) 10.1Titration of GlycineTitration of Glutamic AcidA Sample CalculationWhat is the pH of a glutamic acid solution if the alpha carboxyl is 1/4dissociated?H+ is 1/4 so A- is 1/4 and HA (what’s left) is 3/4. Use the Henderson-Hassebalchequation:pH = pKa + log10[A-]/[HA]pH = 2 + log10(0.25/0.75)pH = 2 + (-0.477)pH = 1.523Titration of LysineAnother Sample CalculationFor each amino group:[NH2] + [NH3+] = 1 x 10-3For the a-amino group9.5 = 9.0 + log10[NH2]/[NH3+]3.16 = [NH2]/[NH3+]So [NH3+] = 0.24mM and [NH2] = 0.76mM76% is present as NH2At pH 9.5, what percentage of the a- and e- amino groups of a 1 mMlysine solution are not protonated?For the e-amino group9.5 = 10.5 + log10[NH2]/[NH3+]0.1 = [NH2]/[NH3+]So [NH3+] = 0.91mM and [NH2] = 0.09mM9% is present as NH2At pH 9.5 the ratio of aNH2 to eNH2 is 8.4:1This is the kind of thing that’s useful to know if you want to do chemistryspecifically at the a-amino group of a peptideReactions of Amino Acids• Carboxyl groups form amides & esters• Amino groups form Schiff bases and amides• Some side chains show unique reactivities– Cys residues can form disulfides and can be easily alkylated– Cys His Asp Glu common metal-binding ligandsSpectroscopic Properties• All amino acids absorb in infrared region• Only Phe, Tyr, and Trp absorb UV• Absorbance at 280 nm is a good diagnostic device for amino acids• NMR spectra are characteristic of each residue in a protein, andhigh resolution NMR measurements can be used to elucidate three-dimensional structures of proteinsUV Absorbance Spectra of Aromatic Amino AcidsPeptides and Proteins: Outline• Proteins as Linear Polymers of Amino Acids• Protein Architecture• Many Biological Functions• Primary Structure DeterminationProteins are Linear Polymers of Amino AcidsWhich looks simple enough, until you see how nature does it…The Peptide Bond…• is usually found in the trans conformation• has partial (40%) double bond character• is about 0.133 nm long - shorter than a typical single bond but longer than a doublebond• Due to the double bond character, the six atoms of the peptide bond group arealways planar!• N partially positive; O partially negativeSix atoms of the peptide group lie in a plane!Peptides• Short polymers of amino acids• Each unit is called a residue• 2 residues - dipeptide• 3 residues - tripeptide• 12-20 residues - oligopeptide• many - polypeptideProteinsOne or more polypeptide chains• One polypeptide chain - a monomeric protein• More than one - multimeric protein• Homomultimer - one kind of chain• Heteromultimer - two or more different chains• Hemoglobin, for example, is a heterotetramer• It has two alpha chains and two beta chains• Insulin - A chain of 21 residues, B chain of 30 residues -total mol. wt. of 5,733• Glutamine synthetase - 12 subunits of 468 residues each - total mol. wt. of 600,000• Connectin proteins - alpha - MW 2.8 million!• b-connectin - MW of 2.1 million, with a length of 1000 nm -it can stretch to 3000 nm!Proteins - Large and SmallThe Sequence of Amino Acids in a Protein…• is a unique characteristic of every protein• is encoded by the nucleotide sequence of DNA• is thus a form of genetic information• is read from the amino terminus to the carboxyl terminusThe sequence of ribonuclease AProtein Architecture• Shape - globular or fibrous• The levels of protein structure- Primary - sequence- Secondary - local structures - H-bonds- Tertiary - overall 3-dimensional shape- Quaternary - subunit organizationWhat Forces Determine the Structure?• Primary structure - determined by covalent bonds• Secondary structure - determined by chirality, steric interactions, and weak forces• Tertiary, Quaternary structures - all determined by weak forces• Weak forces - H-bonds, ionic interactions, van der Waals interactions, hydrophobic interactionsHow to View a Protein?• Backbone


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