Mid 2 BIBC 100

– Monosaccharides (monomer)

• A single polyhydroxy aldehyde or ketone unit

– 5 carbons:

• Riboses (Nucleic acid backbone)

– 6 carbons:

• D-glucose (most abundant 6-carbon sugar, also

called dextrose)

• Fructose (fruit sugar)

• Galactose (milk sugar)

– Oligosaccharides (2-20 monomer)

Disaccharides: 2 monomers

– Sucrose (abundant): D-Glucose + D-Fructose

– Lactose (milk): D-Glucose + Galactose

– Maltose: D-Glucose + D-Glucose

Aldoses

contain an aldehyde

group: the carbonyl is at the end

of the carbon chain.

Ketoses

contain a ketone

group: the carbonyl is at an

internal carbon.

Structual isomer

differ in connectivity:

the atoms are connected in a different order.

• Example: glucose and fructose

• both are hexoses

• glucose is an aldohexose

• fructose is a ketohexose

Stereoisomer

have the same formula and same

connectivity, but differ in 3D arrangement

Chiral carbon

-it is bonded to four different groups.

-Most monosaccharides have these.

-cannot be superimposed on their mirror image (hands)

D/L configuration is determined by the chiral carbon farthest from the carbonyl. If OH is on the …

• If on the RIGHT —> D isomer

• if on the LEFT —> L isomer

Van Hoff rule

-the way we can determine the number of possible stereoisomers

-2^n rule

-the number of chiral centers (n) determines the max stereoisomers

Aldopentoses have _ sterioisomers

8 stereoisomers

Enantiomers are nonsuperimposable mirror images

-Enantiomers are mirror images of each other

-they differ in configuration at every chiral center

Diastereomers are stereoisomers that are not mirror images

-diastereomers have the same chemical formula and atom to atom connectivity

-they are not mirror images

they differ at some but not all chiral centers

Epimers differ at only one chiral center

-epimers are a subtype of diastereomers

-epimers differ at exactly one chiral center

Monosaccharides cyclize in aqueous solution

• Monosaccharides with four or

more carbons can form cyclic

structures.

• Carbonyl C reacts with a hydroxyl

group of the same molecule (often

the second last OH).

• This intramolecular reaction

creates a ring

Pyranoses

sugars with a 6 membered ring (5C + 1 O)

Furanoses

sugars with a 5 membered ring (4C + 1O)

Cyclized sugars are hemiacetals or hemiketals with a new chiral center

• aldehyde + alcohol —> hemiacetal

• Ketone + alcohol —> hemiketal

• if the alcohol is in the same molecules, the rxn forms a ring

• this rxn is the reason why many sugars cyclize in h2o

• the carbonyl carbon becomes a new chiral center for the cyclic sugar

Sugar cyclization creates alpha and Beta anomers

• cyclization creates a new chiral center at the former carbonyl C

• this new chiral center is called anomeric carbon

• the former carbonyl oxygen becomes a hydroxyl group

• if the anomeric OH is opposite to CH2PH (bottom) —> alpha anomer

• if the anomeric OH is on the same side as the CH2PH (top) —> Beta anomer

• the OH oxygen that attacks the carbonyl becomes the ring oxygen

*know how to draw fischer to haworth and vise versa

Polysaccharide linkages determine structure and function

• polysaccharides are long carbohydrate polymers

• unlike proteins and nucleic acids, polysac. are not made from a direct template

• polysacs. have variable length and branching

• storage polysaccharides: commonly have alpha linkages (starch, glycogen)

• structural polysaccharides: commonly have Beta linkages (cellulose, chitin, agarose)

Polysacc.s can be homo or heteropolymers

• homo-polysaccharides: have ONE type of repeating sugar type

• hetero-polysaccharides: have MORE THAN ONE sugar type

Starch contains linear amylose and branches amylopectin

• amylose is a linear a1 to 4 linked glucose polymer

• amylopectin is branches . has a1-4 linked chains with a1-6 branch points

glycogen is a highly branches glucose polymer

• glycogen is the major glucose storage polysaccharide in animals

• it has a1-4 linked glucose chains

• has a1-6 branch points

• glycogen is more branched than amylopectin

• branch points occur roughly every 8-12 residues

Branchin allows rapid glucose release

• Glycogen breakdown enzymes work from chain ends.

• Branching creates many ends.

• More ends allow faster glucose release.

• More branches → more ends → faster mobilization.

storing glucose as glycogen reduces osmotic stress

• keeping free glucose molecules would make big pressure towards blood cells which is bad bc they could rupture

• to prevent this, glucose is turned into glycogen bc it reduces the number of free particles

alpha 1-4 linked glucose chains favor helical conformations

• α(1→4) linkages bend glucose chains

rather than keeping them fully extended.

• Amylose can form a continuous helix with

~6 glucose residues per turn.

• Unbranched segments of amylopectin and

glycogen can form shorter helices; branch

points interrupt them.

• This helical conformation helps pack

glucose compactly for storage.

beta linkages favor STRAIGHT, tightly packed structural chains

• B linked chains are more straight and extended than a linked chains

• extended chains can form many hydrogen bonds, especially inter chain H bonds

• straight chains pack tightly side by side —> strong structural materials

• this contrast with a 1-4 linked storage polymers, which bend into helices

Cellulose is a B 1-4 linked glucose polymer with straight chains

• Cellulose is made of β(1→4)-linked D-glucose units.

• β(1→4) linkages favor extended, relatively straight chains.

• Straight chains can pack side-by-side through many inter-chain hydrogen bonds.

• This tight packing gives cellulose high structural strength.

Humans digest starch but not cellulose because linkage geometry matters

• starch and glycogen contain a 1-4 linkages

• human amylases and glycosidases can hydrolize a-linkages

• and cellulose contains B1-4 linkages

• humans lack enzymes that hydrolyze cellulose B1-4 linkages

• termites and cows rely on symbiotic microbes that produce cellulases

Glucose polymers differ by linkage geometry and branching

chart

Flow of genetic information:

DNA 

• Short for deoxiribonucleic acid

• Stores genetic info in cells and many viruses 

• Double stranded

RNA 

• Short for ribonucleic acid 

• Transfers and interrupts genetic info 

• Other functions 

• Single strand (can fold into tertiary structure)

Flow is: DNA → ← RNA → Protein 

Nucleotides and Deoxy nucleotides both have 3 structural elements: 

1. Pentose sugar 

   1. Ribose or deoxiribose 

2. Nitrogenous base 

   1. Is attached to 1’ C 

3. Phosphate group

   1. 1 or more, attached to the 5’

Which is nucleoTIDE and nucleoSIDE

Nucleoside = base + pentose 

Nucleotide = base + pentose + phosphate(s) 

• Are building block of DNA and RNA

Pentose Component: 

• The pentose is ribose in RNA and deoxiribose in DNA 

• In nucleic acids, they are in the furanose (5) ring form 

  • Ribose has a 2’ - OH 

  • Deoxyr. Has a 2’-H 

• The chemical change affects stability and structure

Nitrogenous Base component: 

• Purines have 2 rings 

• Pyrimidines have 1 ring 

• Bases are planar and aromatic 

• Being planar helps the stack in DNA and RNA

Pyrimidines

• Cytosine (C), Thymine(T), and Uracil(U) are pyrimidines

• All have 6-mem-ring 

• C2: all have carbonyl

• C4: 

  • C: amino 

  • T and U: carbonyl 

• C5: 

  • T: has methyl

Purine

• Adenine (A), Guanine(G) 

• Have 2 rings 

• C2: 

  • G: amino (NH2) 

• C6: 

  • G: carbonyl 

  • A: amino 

• N9 forms sugar C1

Ribonucleotides: RNA building blocks 

• Purines attached to C1’ of the sugar through N9

• Pyrimidines attach to C1’ of the sugar through N1

• C2’ of the ribose has a hydroxyl group attached

• The phosphate is esterified to C5’ of ribose

Deoxiribonucleotides: DNA building blocks 

• Purine N9: to C1’ of deoxyribose

• Pyrimidine N1: to C1’ of deoxyribose 

• C2’ of deoxyribose has a hydrogen 

• The phosphate is esterified to C5’ of deoxyribose

UV light

nucleic acids absorb UV light at 260nm bc of their nitrogenous bases

DNA can have modified bases (minor)

• They are more rare than the standard (major) bases.

• There are 4 types 

• Minor DNA bases can affect gene expression 

Examples: 

• 5 methylcytosine 

• There is methylation in the 5’ C 

• DNA methylation is associated with gene regulation

RNA often times has the modified MINOR bases

• Modified based are common in tRNAs 

• Can support noncanonical base pairing (this means they can form a bunch of diverse structures that can support different functions 

• Modified bases expand RNA structural and functional diversity

Nucleotides perform:

• Genetic information

• Energy carriers 

  • ATP, GTP, etc

• Signaling molecules

  • cyclic forms (AMP, GMP) 

• Cofactors 

  • NAD, FAD

Nucleotides are linked by phosphodiester bonds

The 3’ -OH of one nucleotide forms a phosphodiester bond with the 5’ phosphate group of the next nucleotide

Nucleic acid strands have a 5’ to 3’ directionality 

• Repeating phosphodiester bonds create a nucleotide chain 

• One end has a free 5’ phosphate group

• The other ends has a free 3’ hydroxyl OH group

• DNA and RNA sequences are written 5’ → 3’ 

• The sugar - phosphate backbone is NEGATIVELY charged 

• DNA is more stable than RNA 

  • Reason: 2’ OH of RNA

The 2’ -OH makes RNA less chemically stable than DNA 

• RNA has -OH on the ribose sugar 

• The 2’OH can attack nearby phosphodiester bond 

• This can cleave the RNA backbone 

• DNA lacks the 2’OH, making DNA more chemically stable

double helical structure of DNA

• discovered by watson and crick

  • 2 antiparallel DNA stacks

• Grooves

  • helical twist creates major and minor grooves

  • grooves expose base-pair edges for protein recognition

• chemical architecture

  • hydrophilic exterior : sugar phosphate backbones face OUT

  • base stacking interior: base point inward and stack along the helix axis

Double helical structure of DNA is mainly stabilized by 2 forces 

• Base bair H bonds 

• Base stacking interactions

Base pairing H bonds help hold the 2 DNA strands togther 

• A pairs with T via 2 H bonds 

  • WEAKER 

• G pairs with C via 3 H bonds 

  • STRONGER 

• These standard DNA base pairings are also called Watson Crick pairing 

  • Base pairing is between a purine and a pyrimidine

H bonds form between DONOR and ACCEPTOR groups on the base edges 

• Pairing is between 

  • Nitrogen from main ring —to—- H of Amino group (N-H) 

  • Oxygen of Ketone =O —-to—- H of amino group

Base stacking also stabilizes the DNA double helix 

• DNA bases mostly planar 

• Adjacent bases stack 3.4 A apart 

• Stacking involves pi interactions, van der waals, and hydrophobic effects 

• Stacking acts along the helix axis, perpendicular to base pairing H bonds 

• DNA duplex stability depends on both base pairing and base stacking

DNA melting

heat or extreme pH can denature DNA by separating the two strands

DNA and protein helices use different structural principles

SIMILARITIES: 

• Both are right handed helical structures 

• Both have regular H bond patterns 

• Both directional 

DIFFERENCES: 

• Dna double helix has 2 complementary strands : alpha helix has one polypeptide chain 

• DNA H bonds form between bases on opposite strands; protein alpha helix h bonds form within the same chain 

• DNA bases point inward and stack; protein side chains point outward

DNA can form structures beyond the standard double helix

Palindromic sequences 

• Hairpin structure 

• Cruciform

Hoogsteen base pairing 

• Triple helix 

• Quadruplex

Palindromic DNA sequences

Palindromic DNA sequences can form hairpins and cruciforms 

• When strands separate locally, each strand can pair with itself 

• This creates intra-strand base pairing → stem 

• The intervening sequence forms the loop 

• One strand can form a hairpin 

• Both strands forming hairpins can create a cruciform

Deamination changes base identity 

• Deamination is when it removes an amino group from a base 

• C deaminates to U 

• If left unrepaired, the altered base pairing can cause mutation 

• DNA repair removes inappropriate uracil from DNA 

Which can occur in DNA ? 

• Spontaneous loss of an amino group from the nitrogenous base

• Spontaneous loss of a purine base 

• Crosslinking of two adjacent T bases in the presence of UV light

Depurination removes a base from DNA 

• Hydrolysis can remove a purine base from DNA 

• This creates an abasic site 

• At an abasic site, genetic info is lost 

• Such sites can destabilize or disrupt the dna strand 

Which can occur in DNA ? 

• Spontaneous loss of an amino group from the nitrogenous base

• Spontaneous loss of a purine base 

• Crosslinking of two adjacent T bases in the presence of UV light

G rich DNA can form G-quadruplexes 

• 4 Guanines (G) can form a planar G-quartet 

• G bases interact through Hoogsteen type H bonds 

• Stacked G-quartets form a G -quadruplex 

• This structure forms in g rich sequences 

• Including telomeres and regulatory regions 

• Strands can be arranged parallel or antiparallel 

Thymine dimerization induced by uv light 

• Uv light can covalently link adjacent T bases 

• This forms thymine dimer 

• Thymine dimers distort the dna helix 

• If not repaired, they can lead to mutations 

Thymine dimerization induced by uv light 

• Uv light can covalently link adjacent T bases 

• This forms thymine dimer 

• Thymine dimers distort the dna helix 

• If not repaired, they can lead to mutations

Depurination removes a base from DNA 

• Hydrolysis can remove a purine base from DNA 

• This creates an abasic site 

• At an abasic site, genetic info is lost 

• Such sites can destabilize or disrupt the dna strand 

Depurination removes a base from DNA 

• Hydrolysis can remove a purine base from DNA 

• This creates an abasic site 

• At an abasic site, genetic info is lost 

• Such sites can destabilize or disrupt the dna strand 

Deamination changes base identity 

• Deamination is when it removes an amino group from a base 

• C deaminates to U 

• If left unrepaired, the altered base pairing can cause mutation 

• DNA repair removes inappropriate uracil from DNA 

G rich DNA can form G-quadruplexes 

• 4 Guanines (G) can form a planar G-quartet 

• G bases interact through Hoogsteen type H bonds 

• Stacked G-quartets form a G -quadruplex 

• This structure forms in g rich sequences 

• Including telomeres and regulatory regions 

• Strands can be arranged parallel or antiparallel 

Hoogsteen pairing uses a difference edge of the base 

• Watson crick pairing uses the standard base pairing edge 

• Hoogsteen pairing uses an alternative base edge, often accessible in the major groove 

• A 3rd strand can interact with an existing base pair 

• This can support higher order dna base structures 

Major classes of RNA perform different cellular functions 

• Messenger RNA (mRNA): carries genetic info from DNA to the protein synthesis machinery 5%

• Transfer RNA (tRNA): delivers AA’s to the ribosome during protein synthesis 15%

• Ribosomal RNA (rRNA): forms the structural and catalytic core of ribosomes: 80%

• Regulatory and catalytic RNA’s: include riboswithces, small rna’s, microRNAs’ , interfering RNA, guide RNA, and ribozymes 

*RNA’s have movre diverse functions than DNA bc they can fold into more diverse structures

Base stacking can give single stranded RNA local helical structure

• Adjacent bases interact with one another via base stacking interactions 

• The helical structure would maximize such interactions

RNA’s form secondary structures by intramolecular base pairing 

• RNA secondary structure is driven by intramolecular base pairing 

• Base paired regions are called stems 

• Stems form right handed RNA double helices 

• Unpaired regions form loops and bulges 

• RNA 2* structure is stabilized by H bonding and base stacking

2ndary structure example: tRNA. tRNA folds into a cloverleaf 2ndary structure

• Base pared regions form 4 stems: acceptor stem, D stem, anticodon stem, and TpsiC stem 

• Unpaired regions form 4 loops: D loop, anticodon loop, TpsiC loop, and variable loop 

• The 3’ CCA end carries the amino acid though the ester bond 

• The anticodon loop base pairs with a codon in mRNA

RNA can form standard (watson-crick) base pairs 

• G with C (3 pairs) 

• A with U (2 pairs) 

• Paring with between 

  • Nitrogen front the main ring - H of amino groups 

  • Oxygen of ketones - H of amino groups

RNA nucleotides can also engage in noncanonical interactions (non standard) 

Can occur: 

• Non WatsonCrick (WC) base paring between standard bases: A,U,G,C

• Non WC base pairing between a standard base and a modified base 

• 2’OH mediated H bonds to a base

RNA’s can fold into compact tertiary structures 

• Many RNA’s fold into compact 3D structures under physiological conditions

• RNA tertiary structure organizes stems, loops, and junctions in space

• Folding is supported by base pairing, base stacking, noncanonical interactions, and cations

• Like proteins, many RNA’s have unique 3D structures that are critical for function

RNA backbone flexibility supports diverse conformations 

• Rna has multiple backbone dihedral angles, often labeled a-C (see slide) 

• This flexibility allows RNA stems and loops to pack in different ways 

• Nucleotides can adopt nonhelical conformations and noncanonical interactions 

• This flexibility helps RNA form complex tertiary structures

Cations can help RNA fold into compact tertiary structures 

• RNA phosphate backbones are - charged and repel each other 

• Cations shield phosphate repulsion and allow helices to pack closely 

• Mg2+ can also bind specific sites and stabilize tertiary contacts

tRNA

positions amino acids and anticodon during translation

riboswitches

bind metabolites and regulate gene expression

ribozymes

• catalyze biochemical rns

• the ribosome uses rRNA that regulate gene expression

Riboswitches are RNA sensors that regulate gene expression

• They are RNA elements, often in the 5’UTR of bacterial mRNA’s 

• They bind small molecules such as metabolites, ions, cofactors, or AA’s 

• Ligand binding changes RNA structure 

• The structural change alters transcription or translation of a downstream gene

Ribozymes are folded RNAs with catalytic activity

• Ribozymes are RNAs that catalyze chem rxns 

• Their discovery showed that enzymes are nto always proteins 

• Folded RNA can form active sites that bind substrates 

• RNA active sites can position substrates and catalytic groups to accelerate rxns

Ribozymes catalyze 2 major types of rxns

1. RNa processing rxns 

   1. Breaking and joining RNA phosphodiester bonds 

2. Peptide bond formation 

   1. Linking amino acids during protein synthesis 

Ribosome is a ribozyme 

• The ribsome is a large rna protein machine that synthesizes proteins 

• Its a RNA based catalysis, the rRNA in the ribosome is not a protein component 

• Ribozymes are RNA’s that can catalyze biochemical rxns