Chem 415 Amino Acids and Peptides

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Chem 415 Amino Acids and Peptides
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The Polypeptide backbone

• Peptide Short chain of residues with defined
  sequence ltless than 10 chemistry defined by
  residues
• Polypeptide Longer chain of defined sequence and
  lenghth 10gt lt50100. Chemistry may or may not be
  defined by its residues
• Polyamino acid Random sequence peptide of
  undefined length

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The Polypeptide backbone

• Protein Polypeptides that occur naturally and
  have a definite 3D structure under physiological
  conditions. chemistry is usually more than the
  sum of its parts.

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The Polypeptide backbone
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Amino Acids

• Glycine
• Smallest AA
• Greatest backbone flexability
• Prechiral
• Protein environment is chiral so it is chiral in
  proteins

• Aliphatic Residues
• Ala Val Leu Ile
• Innert carbon side chains
• Dont like water
• Provide much of the DG for protein folding
• Ile has two asymmetric centers
• Unreactive

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Amino Acids

• Proline
• Cyclic Imino Acid
• 2 Amine group
• Often found in cis conformation
• Cis trans conversion is rate limiting in many
  protein folds
• Most restricted conformation in protiens

• Hydroxyl residues
• Ser and Thr
• Hydrophilic
• Found on protein exterior
• Hydrogen bond donor and acceptor
• May be acylated with Acid halides
• Thr has two asymetric centers

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Amino Acids

• Acidic Residues
• Asp and Glu
• Provide general base general acid catalysis
• Hydrophilic
• H bond acceptors at physiological pH
• May be amidated through Carbodimide reaction.

• Ionization state in proteins may be determined by
  reaction with Diazoamide or epoxides
• Small difference in side chain length makes big
  in structural behavior

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Amino Acids

• Amide residues
• Asn Gln
• Amide derivatives of acid groups.
• H bond donor and acceptor
• Polar hydrophilic
• De amidation occurs over time (hydrolysis)
• N Term Gln Cyclizes

• Basic Residues
• Lys
• Hydrophilic
• Weak General acids
• Strong general base
• Good nucleophiles
• Lots of chemicals to label often used in cross
  linking exp.
• TNBS Maleic anhydride o-methyl isourea cyanate
• Reversibly forms shift bases with aldyhides

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Amino Acids

• Basic Residues
• Arg
• Hydrophilic
• Weak General acid
• Reacts reversibly with 1,2 di-ones to form shifft
  bases

• His
• Unique in that has the side chain pKa closest to
  Physiological pH
• Great general acid and general base catalyst
• Great nucleophile when unprotonated
• The most versatile of the amino acids
• Label with DEPC

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Amino Acids

• Aromatic
• Phe Tyr Trp
• Non polar
• Responsible for 280 absorbance of proteins
  http//www.proteinscience.org/cgi/reprint/4/11/241
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• PheltTyrltTrp
• Tyr and Trp major contributers

• Aromatic
• Phe Tyr Trp
• Phe unreactive
• Tyr and Trp react with a variety of reagents
  that label activated Aromatic rings

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Amino Acids

• Met
• Non polar sulfur containing amino acid
• Reacts with CNBr then cyclizes to cleave peptide
  bonds
• reacts with alkylating agents
• Oxidized by molecular oxagen to sulfoxides then
  sulfones.
• Generally non reactive in proteins

• Cys
• Thiol containing amino acid
• easily alkylated
• Forms Disulfide linkages in proteins Cystine
• Will exchange with other sulfides
• Nucleophiles will cleave disulfides