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NUCLEIC ACID :silhouette: (NUCLEIC ACID CHEMISTRY (Non-enzymatic…
NUCLEIC ACID
:silhouette:
BACKGROUND
DNA
C, H, O, N, P
Storage and transmission
Deoxyribonucleotides
Not a protein
Methylated :arrow_right:
minor bases
:arrow_right: regulating/ protecting genetic information
In viral DNA, bases :arrow_right: hydroxy methylated or glucosylated
Backbone is hydrophilic :arrow_right: covalently slow :arrow_right: non-enzymatic hydrolysis of phosphate bonds
5' :arrow_right: 3'
5' end
lack nucleotide
(free PO3 2-)
3' end
lack nucleotide
(free -OH)
Not hydrolyzed under alkali
RNA
C, H, O, N, P
Ribonucleotides
Classes
mRNAs
_ carrying genetic from
DNA :arrow_right: protein
rRNAs
_ component of
ribosomes
tRNAs
_ translates mRNAs :arrow_right: amino acid
Hydrolyzed under
alkali
rapidly
Nucleotides
Nitrogenous base + pentose (B-furanose) + phosphate :arrow_right: heterocyclic compounds
Sugar makes Nucleotide more water - soluble than free bases
Functions
ATP
Linked hormones and extracellular stimuli
Enzyme co-factors and metabolic intermediates
Repositories of genetic information
Phosphodiester linkage 5' :arrow_right: 3'
Nucleoside
Nitrogenous base + pentose (B - furanose) :arrow_right:
pucked
Nitrogenous base
Purine (A, G) :arrow_right: slightly pucked
Pyrimidine (C, T, U) :arrow_right: planar
Highly conjugated molecules
Hydrophobic at pH = 7
At acidic/ alkali pH
, bases changed :arrow_right:
increase Solubility
Resonance :arrow_right: ~ double bonds
Base joined covalently
N - B - glycosyl bond
N - 1 of pyrimidine
N - 9 of purine
Weak forces
H-bonding
= amine + carbonyl
Complementary of >=2 strands
A=T (U), G=C
Tauromerization
Keto
(U, T, G) predominant at pH=7
Enol
(C) predominant at pH=7
Cytosine also undergoes
Amino :arrow_right: Imino
Base -stacking interaction
= van der waals + dipole - dipole interaction
Minimize contact of bases with water
Stabilizing 3-D strcture
NUCLEIC ACID STRUCTURE
Background
3 layers
Primary
_nucleotide sequence
Secondary
_stable sequence
Tertiary
_complex folding chromosomes within chomatin and nucleoids
DNA stores genetic information
DNA molecules have
distinctive base
compositions
4 nucleotide bases occur in # ratios and closely related
Varies among species
Different tissue of same species :arrow_right: same bases
Do not change
A + G = T + C (Chargaff ' s rule)
DNA is = helix
H - bonds
Base - stacking interaction
DNA occurs in different 3-D forms (rotation)
Rotate bond #4 :arrow_right: endo/exo
Rotate bond #7 :arrow_right: anti/syn
Purine = anti/syn
Pyrimidine = anti
Watson - Crick model
2 anti-parallel helical DNA chain :arrow_right: = helix
Backbone :arrow_right: hydrophilic :arrow_right: outside
C2' endo conformation
Bases inside
Major groove and minor groove
A=T, G=C
Each plane is 3,4A apart
1 turn = 10 base pairs (34A )
B-form
Most stable _random sequence :arrow_right: physical condition
Right handed
1 turn = 10.5 base pairs
Sugar :arrow_right: C2' endo
Base :arrow_right: Anti
A-form
More common :arrow_right: Crystallization
Right handed
Helix is wider
1 turn = 11 base pairs
Sugar :arrow_right: C3' endo
Base :arrow_right: Anti
Major groove _deeper, minor groove_shallower
Z-form
More slim and elongated
Left handed
1 turn
=
12
base
pairs
Sugar
C2' endo_pyrimidine
C3' endo_ purine
Base
:arrow_right: Anti_pyrimidine, Syn_purine
Minor groove_narrow and deep
Unusual structures
Sequence dependent :arrow_right: affect function and metabolism
Palindrome (identically)
Examples: rotator and nurse run
Palindromic DNA :arrow_right:
inverted repeats over 2 strands
Hairpins and Cruciforms
formed by self-complement_palindromic
Inverted repeat within individual strands :arrow_right:
mirror repeats
Not complementary same strands :arrow_right: no hairpin/cruciform
Recognition sites for DNA binding proteins/ enzymes
Hoogsteen base pairing
Triplex
Purine + pyrimidine = Hoogsteen base pairing
Purine + pyrimidine = Watson-Crick base pairing
Most stable at low pH
Quadruplex
:arrow_right: G residues :arrow_right: very stable :arrow_right: antiparallel, parallel
H-DNA
:arrow_right: regulating gene expression
Synthetic DNA
:arrow_right: form triplex :arrow_right: disrupt gene expression
NUCLEIC ACID CHEMISTRY
Extreme pH and T>80
:arrow_right: disruption of H-bonds and base stacking
Loss in base stacking :arrow_right: rise absorption UV light =
Hyperchromic effect
Melting T
=
50% DNA denatures
Higher G=C
(3 H-bonds):arrow_right: need more E to dissociate :arrow_right:
higher Mp
RNA
duplexes more
stable
than DNA
duplexes as it has higher T
Non-enzymatic transformation
Slow
Mutation
linked aging and carcinogenesis
Deamination
= loss of NH2 group :arrow_right: preservative of food (HNO2)
Hydrolysis of N-B-glycosyl bond :arrow_right: higher rate for purines :arrow_right:
Depurination
DNA not stable in acid (apurinic acid)
RNA stable in dilute acid
Unrepaired U:arrow_right: reduce G=C :arrow_right: U is methylated to T, U=A is less stable than A=T :arrow_right: reduce mutation frequency in DNA
Hybdrization
Complementary strands formation
Closer evolution related :arrow_right: more extensively DNA hybridized
Application: crime detection and prediction of disease
UV light
form a cyclobutane ring :arrow_right:
10% DNA damage
Ionizing radiations
(x rays, gama rays,..) :arrow_right:
10% DNA damage
Oxidative reagents
_
-OH radicals
during irradiation/ byproduct of aerobic metabolism :arrow_right:
DNA damage
DNA is only macro that has repair system
Methylation of C
Embryonic development
Epigenetics
_ behavior change by environment without changing in nucleotide sequences
Nucleic acids can be synthesized chemically
(4 steps)
RNA
In nucleus and cytoplasm
Increase protein synthesis :arrow_right: rise its rate turnover
Carry gene DNA :arrow_right: protein
No simple, regular structure
Base pairing with RNA/DNA
A=U, G=C (G=U :arrow_right: unusual in DNA, common in RNA)
RNA - DNA :arrow_right: antiparallel
Base stacking interactions
Purine-purine > purine-pyrimidine > pyrimidine-pyrimidine
Complementary sructures
Predominant = A-form
High salt, high T = Z-forrm
Bulges, internal loops
Hairpins, most common :arrow_right: stable, tight lopps
mRNAs
Prokaryote
Code 1 polysaccharide =
Monocistronic
Code >=1 polysaccharides =
Polycistronic
Synthesis
many proteins
Eukaryote
Most
monocistronic
Synthesis
1 protein
but composed of introns and exons
hnRNA = introns + exons + poly A
Longer = 3x polypeptide as non - coding sequence
Right handed, single strand
tRNAs
= carrying a.a :arrow_right: self-pairing and unusual H- bonding, small chains