Biomol2

Biomolecules Chemical principles that are components and functions in living organism. Biomolecules that are the major constituents of cells Proteins: long polymers of amino acids Nucleic acids (DNA and RNA): polymers of nucleotides Polysaccharides: polymers of simple sugars Lipids: building from glycerol and fatty acids

Stereospecificity of biomolecules is important to catalytic functions. •In living organisms, only one form of isomers of biomolecules can be employed as components and functions. •Proteins or enzymes can only bind to specific isomers, D-isomer form of sugar or L-isomer form of amino acid. •Compounds of carbon commonly exist as stereoisomers.

Subdivision of isomers

Enantiomer (chiral molecules)

Diasteroisomer

Chirality A chiral object has a mirror image that is different from the original object (for not chiral, being called achiral)

Indicate whether the following objects are chiral or achiral.

Enantiomers A pair of enantiomers is always possible for molecules that contain one tetrahedral atom with four different groups attached to it.

Chiral molecules

Achiral molecules Behind the plane C

Upward out of the plane

Line in the plane

Nomenclature of Enantiomers: The (R-S) System Cahn-Ingold-Prelog system or (R-S) system I Assign a priority of each substitute group based on atomic number

If can not make decision, use the next Atoms along the chain as tiebreakers.

Cahn-Ingold-Prelog system or (R-S) system

H 1 C Br

CH3 3 C CH3

H 5

H

CH3

CH3

C CH3

H 2 C Cl

H

C CH2 F

H 6 C CH3

Cl

CH3

H

4

In case of double and triple bond, treat them as a single bond to a separate atom.

Nomenclature of enantiomers: the (R-S) System II Rotate the formula so that the group with lowest priority is directed away from us.

III Draw an arrow from first priority group, through the second, to third Clockwise (R, rectus) Counter clockwise (S, sinister)

Nomenclature of enantiomers: the (R-S) System

Interactions between biomolecules are stereospecificity. •In living organism, chiral molecules are usually present in only one from of their chiral forms. •Glucose occurs biologically in the D isomer. •Amino acids occur only as L isomer.

The ability to distinguish between stereoisomers is a properties of enzymes and other proteins and a characteristics feature of the molecular logic of life.

Classification of carbohydrates •The simplest carbohydrates are the monosaccharides •Sugars or saccharides (Latin saccharum, Greek sakaron) •General formula is (CH2O)n, carbohydrate-hydrates of carbon •Carbohydrates are usually defined as polyhydroxy aldehydes or polyhydroxy ketones O

O

Aldehyde group C

C

H

ketone group

Monosaccharides: the simplest carhohydrates Disaccharides: monosaccharide + monosaccharide Oligosaccharides: polymers of 2-10 monosaccharides Polysaccharides: > 10 monosaccharides

Classification of monosaccharides Monosaccharides are classified according to I The number of carbon atom (triose, tetrose, pentose) II Group containing in molecules Adehyde: aldose Ketone: ketose Combination of two classifications: aldotetrose, ketopentose

Enatiomers contain optical activity.

polarizer

Polarized light

Polarimeter is used to determine optically active compounds.

Enantiomer that rotates the polarized light: Clockwise (+), dextrorotatory (dexter = right) Counterclockwise (-), levorotatory (laevus = left)

Configuration and the plane-polarized light

-No correlation exists between configuration of enantiomers and the direction (+ or -) of plane-polarized light. -No necessary correlation exists between the (R) and (S) and the direction (+ or -) of plane-polarized light.

D and L designations of monosaccharides The simplest monosaccharides are glyceraldehyde and dihydroxyacetone CHO CHOH CH2OH

Glyceraldehyde (aldotriose)

CH2OH HC O CH2OH

Dihydroxyacetone (ketotriose)

R-S system: (+)-Glyceroldehyde is (R) (-)-Glyceraldehyde is (S)

(+)-glyceraldehyde is designated D-(+)-glyceraldehyde and (-)-glyceraldehyde is designated L-(-)-glyceraldehyde. Both compounds serve as configurational standards for all monosaccharides.

D and L designations of monosaccharides A momacharides whose the highest numbered stereocenter (the penultimate carbon) has the same configuration as D-(+)-glyceroldehyde is designated as a D sugar. Draw vertically with ketone or aldehyde group at or nearest the top. D sugar is designated when the hydroxyl group is on the right.

D and L isomers are like (R) and (S) in that they are not related to optical rotation because it is only one designed for the penultimate carbon - that may encount other sugars that are D-(+) or D-(-) and ones that are L-(+) or L-(-).

Structural formulars for monosaccharides Fischer projection

Emil Fischer (1852-1919)

D-(+)-glucose primarily exists in equilibrium with two cyclic forms. The cyclic forms of D-(+)-glucose are hemiacetal formed by an intramolecular reaction of the –OH group at C5 with aldehyde group of C1. Cyclic form

Linear form

The addition of alcohols: hemiacetals and acetals Hemiacetal An aldehyde or ketone in an alcohlol causes the slow of an equilibrium establishment between these two compounds and a new compound called a hemiacetal.

The hemicaetal is resulted from nucleophilic addition of the alcohol oxygen to the carbonyl carbon of aldehyde or ketone.

The addition of alcohols: hemiacetals and acetals Hemiacetal

Cyclic form of D-glucose

Ketone group of ketose undergo similar reaction in an alcohol Hemiketal

Hemiketal

Diastereoisomer of two cyclic forms

α α anomer: -OH is on the opposite side of the ring from –CH2OH

β β anomer: -OH is on the same side of the ring from –CH2OH

•Cyclization creates a new sterocenter at C1(diasteroisomer). •In carbohydrate chemistry diasteroisomers of this type are called anomers, and the hemiacetal carbon atom is called anomeric carbon. •Structure representing anomers are called Haworth formulas. •Each anomer is designed as an α anomer and β anomer.

The actual conformation of D-glucose Studies of the structure of cyclic form of D-glucose using x-ray crystallography have demonstrated that the rings are the chair forms.

O

Pyran

The six-member ring O

Furan

The five-member ring

Aldohexoses also exist in fivemembered ring. However, the aldopyranose ring is much more stable than the aldofuranose and predominates in six-membered ring.

Mutarotation -OH axial

-OH equatorial

-The concentration of open-chain D-glucose at equilibrium is very small (negative test for Schiff’s reagent). -β-anomer is more stable than α-anomer for D-glucose but this is not necessary because with D-mannose, the equilibrium favors the α-anomer.

Monosaccharides are reducing agents. •Benedict’s reagent (an alkaline solution containning a cupric citrate complex ion) and Tollen’s solution [Ag(NH3)2OH] can oxidize and give positive test with aldose and ketose. •Sugars positive test are known as reducing sugars: all carbohydrates that contain a hemiacetal group give positive test all carbohydrates that contain only acetal group do not give positive test.

No equilibrium in aldehydes or α-hydroxy ketones

Monosaccharides are reducing agents. •Cu2+ can oxidize only aldose but in alkaline solution, ketose convert to aldose. •The oxidation only occurred in noncyclic forms but they are still enough for reacting to alkaline copper solution and this can perturb equilibrium to produce more Haldehydes or O α-hydroxy ketones. CH2OH C OH C H •Positive test provides C O C OH HC OH OHOHbrick-red precipitate (CHOH)n (CHOH)n (CHOH)n O

CH2OH

CH

C O

(CHOH)n

or

(CHOH)n

CH2OH

CH2OH

Aldose

Ketose

CH2OH

CH2OH

CH2OH

Ketose

Cu2+

Cu2O + Oxidized Products

Isomers of monosaccharides -A molecule with n chiral centers can have 2n stereoisomers. -Two isomer molecules that are not mirror images or not enantiomer are called diastereoisomer. -Two sugars that differ only in the configuration of one carbon atom are called epimer. H O C H C

O

H C OH CH2OH

D-Glyceraldehyde

21 isomers

H C OH HO C H H C OH H C OH CH2OH

D-Glucose

24 isomers

Disaccharides Disaccharides such as maltose, lactose and sucrose consist of two monosaccharides covalently link by o-glycosidic bond. •O-glycosidic bond is formed by ahydroxyl group of one sugar reacting with the anomeric carbon of the other. •This bond can be hydrolyzed by acid but resist cleavage to base. •Anomeric carbon involving in glycosidic bond can not be oxidized by cupric or ferric ion thus, in disaccharides or polysacharides, the end of chain be oxidized and called reducing end

Disaccharides -occurs naturally in milk

Reducing sugars Nonreducing sugars -energy storage in hemolymph of insect

Nonreducing sugars

-formed by plants but not animals

Polysaccharides •An another name is glycan. •Polymers can be occurred with or without branching. Two types of polysaccharides: •homopolysaccharides contain only single type monomer. -Food storage for monosaccharides, starch and glycogen -Structural element, cellulose or plant cell wall and chitin for exoskeleton •heteropplysaccharides contain two or more different kinds. -extracellular support (extracelluar matrix component) for organism of all kingdom homopolysaccharides

heteropolysaccharides

Polysaccharides Strach (storage polysaccharide in plant) -Two types >Amylose: glucose polymer that D-glucose residues are liked by α(1-4) linkages >Amylopectin: similar to amylose but higher molecular weight with branch points at α(1-6) linkages Glyogen (storage polysaccharide in animal) >Main storage in liver and skeletal muscle >Structure is similar to amylopectin but more extensively branched

Polysaccharides Structural conformation of starch or glycogen

Polysaccharides Dextran (bacterial and yeast polysaccharides) •Polymer of D-glucose that are linked by α(1-6) with branching at α(1-3) and some points at α(1-2) α(1-4) •Dental plaque is composed of dextran produced by oral bacteria on tooth surface. Cellulose •Structural component in plants, cell wall, trunk, woody portion and stalks. •Polymer of D-glucose in βconfiguration with β (1-4) linkages •Most animals can not use cellulose as fuel source because they have no enzymes to degrade bond of β (1-4)

Polysaccharides Structural conformation of dextran and cellulose

•Cellulose is extended structure with lying side by side of several chains. •Structure is stabilized by interchain and intra chain hydrogen bonds.

Polysaccharides Chitin •linear chain of homopolysaccharide •Polymer of N-acetylglucosamine linked by β (1-4) configuration •Animal enzymes can not hydrolyze chitin •Component of hard skeleton in arthropod, insects, lobsters and crabs

Polysaccharides Agar •Natural products from marine red algae and some sea weeds •Sulfated heteropolysaccharides of D-galactose and L-galactose •L-galactose has ether linkage between C3 and C6. •Unbranched polymers: agarose •Branched polymers: agaropectin •Gel-forming properties

Amino acids, peptides and three dimensional of proteins •Proteins are polymers of amino acids. •All proteins are the combination of 20 amino acids in differences of sequences resulting in differences of function and properties. General structure of amino acids α carbon, chiral center

H +

H3N

C

COO-

First carbom atom of carboxylic group, which is deprotonated form at physiological pH

R Amino group is protonated at physiological pH.

Side chains which vary in structure, size and electric charge

D and L forms of amino acids

•L-isomers of amino acids are remarkable found in living organisms. •D-amino acid residues can be found only in a few, small peptides, bacterial cell walls and peptide antibiotics. •Enzymes synthesizing amino acids in living organisms contain asymmetric active sites and cause stereospecificity.

Classification of amino acids according to R group

Glycine has no optical activity.

Classification of amino acids according to R group

Classification of amino acids according to R aroup

Amphotoric properties of amino acids

Amino acids have a diprotic acid, monoamino and monocarboxylic group (ampholyte).

Fully protonated

Zwitterion

Fully deprotonated

Priority in deprotonation of amino and carboxylic group

Titration curve of amino acids •At pH point of inflection between two stages of one positive charge group and one negative charge group results in no net charge. •The pH that affects on both groups resulting in No net charge is called pI. pK a = − log K a

pK a1 + pK a 2 pI = 2

Titration curve of amino acids In case of ionizable R group

Peptides •Protein is a polymer of amino acids covalently linked by peptide bonds (amide bond). •The direction of protein is always indicate from N-ter minus to C-terminus. •N-terminal, C-terminal and R group only distribute the charge. H3C

CH3 CH

CH2OH +

H3N

C

C

H

O

H N

N-terminal (amino)

H C

C

H

O

H N

CH2 C

C

H

O

H N

CH3 C

C

H

O

H N

CH2 C

C

H

O

O-

C-terminal (carboxylic)

Direction of peptides •Find the position of peptide bond •Imagine in the peptide bond cleavage and see on right side of the end group whether it is amino or carboxylic H3C

CH3 CH

CH2OH +

H3N

C

C

H

O

H N

H C

C

H

O

H N

CH2 C

C

H

O

H N

CH3 C

C

H

O

CH2

H N

C

C

H

O

O-

CH3

H3C CH

CH2 -

O

C

C

O

H

H N

CH3 C

C

O

H

H N

CH2 C

C

O

H

H N

H C

C

O

H

H N

CH2OH C

C

O

H

NH3+

Peptide bond structures

•In x-ray crystallography studies, C-N is shorter than C-N bond in simple amine. •The atom of Cα, C-carbonyl group, N and –H are coplanar in trans. •This characteristics is come from resonance hybrid between oxygen and N atom. •C-N bond can not freely rotate whereas Cα-C and N-Cα are permitted.

Levels of protein structures •Primary structure: the sequences of amino acid residues •Secondary structure: stable arrangements of amino acid residues forming specific patterns •Tertiary structure: three dimensional arrangements of specific patterns •Quaternary structure: arrangements of polypeptide subunits when a protein has more than one polypeptide

Protein secondary structure Helical structure (α-helix) •Tightly wound polypeptide backbone in right handed direction •R groups (side chains) protrude out from the helical backbone •Structure is stabilized by intramolecular hydrogen bond between C=O and N-H of polypeptide backbone. N (+) 3.6 residues per turn

C (-) Cross-section view

Protein secondary structure

β conformation •The backbone of polypeptides arrange similar to pleats (β sheet) in zigzag pattern. •The structure is stabilized by intermolecular hydrogen bond of adjacent peptides (two-type arrangements, parallel and antiparallel). •R groups (side chains) protrude from zigzag conformation is opposite directions.

More stable (shorter distance of H-bond)

Protein tertiary structure

α+β

α helix

β sheet

•Some proteins contain only helical, only sheet and combination of both types of secondary structure. •Three dimensional structure can be stabilized by weak interactions such as hydrophobic, ionic interaction, hydrogen bond, which are formed by side chain residues. •The strong stabilization can be also formed by covalent linkage of disufide bond (S-S) between cystein residues at different positions in polypeptide.

Protein tertiary structure

Quaternary structure •Some proteins consist of more than one polypeptide chain, called multisubunit. •Individual subunit can be identical or different. •Oligomer: different subunit, heterodimer, heterotetramer •Protomer: identical subunit, homodimer, homotetramer •Most of quaternary structures are stabilized by noncovalent interaction: a few proteins that subunits are covalently linked such as insulin

Hemoglobin: heterotetramer (α2β2)

subunit