Amino Acids and Peptides Precursors of Proteins

Proteins (Amino Acids) Only 20 naturally-occurring amino acids Only linear structures

Functions of Proteins I Catalysts and Metabolic Regulation – Enzymes Protection –Serum antifreeze proteins –Blood coagulation –Antibodies Membrane Transport – Nutrients Signal Transduction – Cell Surface Receptors Structural Support – Collagen

Functions of Proteins II Coordinated Motion – Muscle Contraction Genetic Regulation – DNA Binding Proteins Transport – Hemoglobin Generation and Transport of Nerve Impulses Nutrient Storage –Seed proteins –Casein in milk

Function of proteins largely due to properties of constituent amino acids

Standard Amino Acids (20)

Stereochemistry Review Optical Activity

Figure 4-9 Diagram of a Polarimeter

Rotation of Plane of Polarized Light Dextrorotatory (rotation to the right) = “d” or “+” Levorotatory (rotation to the left) = “l” or “-” Empirical

Optically Active Molecules are Asymmetric (i.e. not superimposible on their mirror image)

Chiral (Asymmetric) Carbon Four different substituents Stereoisomers C  atoms of amino acids (except glycine) are asymmetric centers!

Chiral Centers Give Rise to Enantiomers (non-superimposible mirror images)

Distinguishing Stereoisomers Rotation of plane of polarized light (not related to absolute configuration) Cahn-Ingold-Prelog Method (R/S) Fischer Method (projections)

Cahn-Ingold-Prelog Method (R/S) (1956)

Fischer Convention (1891)

Protein Amino Acids

Fischer Method/Projections (L/D)

L -  -Amino Acids

Chirality and Biochemistry Life is Based on Chiral Molecules Biosynthetic processes almost invariably produce pure stereoisomers – e.g. L -amino acids

Biological D-amino acids: Bacterial Cell Wall

Pharmaceutical Industry Racemic Mixtures

Figure 4-12 Benign

Figure 4-13 Devastating

Chiral Synthesis Goal of Organic Chemistry

Amino Acids

Non-Polar Hydrophobic Amino Acids

Aromatic Amino Acids Non-Polar Polar

Polar Amino Acids

Negatively Charged (Acidic) Amino Acids

Positively Charged (Basic) Amino Acids

Notation for 20 Standard AAs

Figure 4-8 Greek Nomenclature

Dipolar Ions (Zwitterions)

Amino Acids can be Buffers

Histidine is particularly important for biological function

Isoelectric point (pI) pH at which the molecule has a net charge of 0. pI = pKa 1 + pKa 2 2 –Using the pKa’s on either side of the neutral species

The Peptide Bond

Peptide Bonds Linear Polymers N- Terminus C- Terminus

Peptides Dipeptides Tripeptides Oligopeptides Polypeptides

Diversity Number = 20 n

Variations in length and sequence contribute to the diversity of shapes and biological functions of proteins

Nomenclature of Peptides (Primary Structure) L-alanyl-L-seryl-L-aspartic acid [aspartate] Alanylserylaspartate AlaSerAsp ASD

Diversity (Tripeptide: 3 x 2 x 1 = 6 arrrangements) Ala Ser AspAla Asp Ser Ser Ala AspSer Asp Ala Asp Ser AlaAsp Ala Ser For 20 amino acids (small peptide): 20! = 2.43 x 10 18

Selenocysteine: the 21 st Amino Acid

Pyrrolysine: the 22 nd Amino Acid

Protein Amino Acid Derivatives

Figure 4-14 Some Modified Peptidyl Amino Acids

Disulfide Bond Formation (Cystine)

Hydroxylation

Phosphorylation

Acetylation

Formylation (amino terminal methionine)

Other Modifications Methylation (methyl group) Glycosylation (sugar)

Figure 4-15 Biologically Active Amino Acid Derivatives

Non-protein Amino Acids

Green Fluorescent Protein

Box 4-3 figure 1 Aequorea victoria

Box 4-3 figure 2

Green Fluorescence Protein (GFP) GFP cloned in the early 1990s and expressed in E. coli.

GFP-like and GFP variants GFP-like proteins identified in non- bioluminescent organism (i.e. corals) Mutants with faster and brighter fluorescence have since been identified.

In vivo Imaging Spatial-temporal imaging of bacterial infection Zhao, M. et al. PNAS. 2001; 98(17):

Cool Green Things!