Darrell R. Davis Department of Medicinal Chemistry Translation and tRNAs.
Chem 109 C Bioorganic Compounds · 2019-12-02 · tRNAs are amino acid carriers. rRNA - part of...
Transcript of Chem 109 C Bioorganic Compounds · 2019-12-02 · tRNAs are amino acid carriers. rRNA - part of...
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Fall 2019HFH1104
Armen ZakarianOffice: Chemistry Bldn 2217
Chem 109 CBioorganic Compounds
http://labs.chem.ucsb.edu/~zakariangroup/courses.html
CLAS Instructor: Dhillon [email protected]
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Average 49.1St Dev 14.1
Max 87.5
Min 15
Midterm 3 stats
test are available outside room 2135 (Chemistry, 2nd floor)in a box, sorted in alphabetical order, by color
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Each test will be curved individually to 75% average
Lowest midterm will be dropped
Scores from 2 best M and the Final will be added
Grades will be assigned according to the syllabus
Final Course Grading
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22. 11 ptDraw all reactions required to convert hexanoic acid to 3 molecules of acetyl CoA through the β-oxidation cycles. Name all necessary coenzymes and enzymes. How many molecules of ATP and CO2 will be produced from hexanoic acid after its entire metabolism through all 4 stages ?
O
O
hexanoic acid (hexanoate)
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Overview
OVERVIEW o structures of DNA vs. RNA - riboseo structures of bases: Adenine, Uracil/Thymine, Guanine, Cytosine. “Enol forms”o hydrogen bonding between A-T(U) and G-C. H-donors/acceptorso Base complementarityo RNA strand cleavage assisted by the 2’-OH group in the ribose unit (cyclic PDE)o Deamination: RNA genetic instabilityo DNA replicationo RNA synthesis: transcription. Template strand (read 3’ to 5’). Sense strand and
the RNA primary structure (T −> U).o Protein synthesis: translation. mRNA determines the amino acid sequence.
tRNAs are amino acid carriers. rRNA - part of ribosomes
o no section 26.12, 26.13
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DNA, RNA, etc. Structure and Classification • DNA: Deoxyribonucleic acid
encodes hereditary information controls cell division and growth
• RNA: Ribonucleic acid
transcription and translation stores genetic information in viruses
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DNA, RNA, etc. Structure and Classification
Obase
O
O
Obase
O
O
PO O-
PO O-
Obase
O
O
2'
5'
PO O-
DNA
Obase
OHO
OP
Obase
OHO
O
PO O-
PO O-
Obase
OHO
O
O O-
2'5'
RNA
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DNA, RNA, etc. Structure and Classification
DNA and RNA RNA only
DNA only
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DNA, RNA, etc. Structure and Classification
DNA and RNA RNA only
DNA only
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DNA, RNA, etc.
DNA and RNA RNA only
DNA only
Structure and Classification
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DNA, RNA, etc.
DNA and RNA RNA only
DNA only
Structure and Classification
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DNA, RNA, etc.
DNA and RNA RNA only
DNA only
Structure and Classification
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DNA, RNA, etc.
DNA and RNA RNA only
DNA only
Structure and Classification
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DNA, RNA, etc. Structure and Classification
nucleosides = base + sugar
ON
NN
N
NH2
HO
HO
2'-deoxyadenosine
ON
NN
N
NH2
HO
OHHO
adenosine
PRACTICE PROBLEM Draw the structures and provide names for all other nucleosides
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DNA, RNA, etc. Structure and Classification
nucleotides = base + sugar + phosphate
2'-deoxyguanosine5'-monophsphate
guanosine3'-monophosphate
O
N
NHN
N
O
O
HO
P-OO-
OH2N
O
N
NHN
N
O
HO
O
H2N
OH
O
N
NHN
N
O
O
O
P-OO-
OH2N
OH
PO-
O O- POO-
O-
a deoxynucleotise
a ribonucleotide
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DNA, RNA, etc. Structure and Classificationnucleotides = nucleoside phosphates
cytidine5'-triphosphate
ON
O
OHHO
POO-
OPO
OO-
PO
-OO-
N
NH2
OON
O
OHHO
POO-
O
N
NH2
O
cytidine5'-monophosphate
CMP CTP
dAMP2’-deoxy Adenosine Mono Phosphate
PRACTICE PROBLEM 2 Draw the structures for: dCMP, UDP, dTTP
2'-deoxycytidine5'-monophosphate
dCMP
ON
O
HO
POO-
O
N
NH2
O
dCDP
ON
O
HO
POO-
OPO
-OO-
N
NH2
O
2'-deoxycytidine5'-diphosphate
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DNA, RNA, etc. Structure and Classification
dinucleotides 2 nucleotides oligonucleotides 3-10 nucleotides polynucleotides many (human DNA - 3,100,000,000 bp)
dCTP
ON
O
HO
POO-
OPO
OO-
N
NH2
O
ON
NN
N
NH2
O
HO
POO-
OPO
OO-
PO
-OO-
P-O
O
O-+
dATP
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DNA, RNA, etc.
ON
O
O
POO-
OPO
OO-
N
NH2
OP-O
O
O-
POO
O-
O N
HO
N
N
N
NH2O-P
O
OO-
PO
-OO-
+
CAGTAACCTGAGAACCAATCGGAA…
Synthesis: nucleotide triphosphates, 5’ 3’
DNA or RNA polymerase
primary structure
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DNA, RNA, etc.
Facts about DNA
! double helix
! two anti-parallel strands
A pairs with T, G pairs with C
pairing through hydrogen bonds
stacking interactions
3’
5’
5’
3’
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DNA, RNA, etc.
Facts about DNA
double helix
two anti-parallel strands
! A pairs with T, G pairs with C
pairing through hydrogen bonds
stacking interactions
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DNA, RNA, etc.
Facts about DNA
double helix
two anti-parallel strands
A pairs with T, G pairs with C
! pairing through hydrogen bonds
stacking interactions
NN
O
O
R
ribose
HN
N N
NN
ribose
HH
R-CH3, thymine adenine
2 hydrogen bonds
NN
N
ribose O
HH
NN N
NO
NH
H
Hribose
cytosine guanine
3 hydrogen bonds
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DNA, RNA, etc.
Facts about DNA
double helix
two anti-parallel strands
A pairs with T, G pairs with C
pairing through hydrogen bonds
! stacking interactions
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DNA, RNA, etc.
PRACTICE PROBLEM 4 and 5 Indicate which functional group of the five heterocyclic bases can function as a hydrogen bond donor (D), a hydrogen bond acceptor (A), or both (D/A) How would the base pairing be affected if the bases existed in the “enol” form?
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DNA, RNA, etc.
PRACTICE PROBLEM 4 and 5 Indicate which functional group of the five heterocyclic bases can function as a hydrogen bond donor (D), a hydrogen bond acceptor (A), or both (D/A) How would the base pairing be affected if the bases existed in the “enol” form?
NN
O
O
R
ribose
HN
N N
NN
ribose
HH
R-CH3, thymine adenine
A A
AA
D
D
A
NN
N
ribose O
HH
NN N
NO
NH
H
Hribose
cytosine guanine
A A
A
A
A
D
D
D
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DNA, RNA, etc.
PRACTICE PROBLEM 4 and 5 Indicate which functional group of the five heterocyclic bases can function as a hydrogen bond donor (D), a hydrogen bond acceptor (A), or both (D/A) How would the base pairing be affected if the bases existed in the “enol” form?
NN
O
O
R
ribose
HN
N N
NN
ribose
HH
R-CH3, thymine adenine
A A
AA
D
D
A
NN
O
O
R
riboseN
N N
NN
ribose
HH
R-CH3, thymine adenine
D A
AA
D
A
H
A
“enol” form of T
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DNA, RNA, etc.
PRACTICE PROBLEM 4 and 5 Indicate which functional group of the five heterocyclic bases can function as a hydrogen bond donor (D), a hydrogen bond acceptor (A), or both (D/A) How would the base pairing be affected if the bases existed in the “enol” form?
NN
N
ribose O
HH
NN N
NO
NH
H
Hribose
cytosine guanine
A A
A
A
A
D
D
D
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DNA, RNA, etc.
PRACTICE PROBLEM 7 If one of the strands of DNA has the following sequence of bases running in the 5’ → 3’ direction,
GGACAATCTGC a. what is the sequence of bases in the complementary strand? b. what base is closest to the 5’-end in the complementary strand?
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DNA, RNA, etc.
DNA is stable, RNA is not: chemical stability
Obase
OHO
OP
Obase
OHO
O
PO O-
O O-
2'5'
RNA
Obase
OO
OP
Obase
OHO
O
P-O O-
O O-
:B
B H
Obase
OO
OP
PO-
O O-
O
Obase
OHO
OH
2',3'-phosphodiester
+
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DNA, RNA, etc.
Obase
OHO
OP
Obase
OHO
O
PO O-
O O-
2'5'
RNA
Obase
OO
OP
Obase
OHO
O
P-O O-
O O-
:B
B H
Obase
OO
OP
PO-
O O-
O
Obase
OHO
OH
2',3'-phosphodiester
+
DNA is stable, RNA is not: chemical stability
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DNA, RNA, etc.
DNA is stable, RNA is not: genetic stability
DNA has thymine, RNA has uracil
N
N
NH2
O
RNAcytosine
H2O N
N
OH
OR
tautomerizationHN
N
O
O
RNAuracil
MUTATION !
spontaneous deamination
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DNA, RNA, etc.
DNA is stable, RNA is not: genetic stability
DNA has thymine, RNA has uracil
N
N
NH2
O
RNAcytosine
H2O N
N
OH
OR
tautomerizationHN
N
O
O
RNAuracil
MUTATION !
N
N
NH2
O
DNAcytosine
H2O N
N
OH
OR
tautomerizationHN
N
O
O
DNAuracil, NOT found
in DNA
HN
N
O
O
DNA
NOT recognized asdefect and repaired
spontaneous deamination
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DNA, RNA, etc.
spontaneous deamination
NH
N
O
NH2
NH
NH
O
OH2O
+ NH3
cytosine
PRACTICE PROBLEM 16 Adenine can be deaminated to hypoxanthine, and guanine can be deaminated to xanthine. Draw structures for the deamination products.
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DNA, RNA, etc. DNA (bio)synthesis
! is called replication
! done by DNA polymerase
strand separation, replication fork
again, always in 5’ → 3’ direction
using the nucleotide triphosphates
X-ray structure of rb69 gp43 + thymine glycol
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DNA, RNA, etc. DNA (bio)synthesis
! is called replication
! done by DNA polymerase
strand separation, replication fork
again, always in 5’ → 3’ direction
using the nucleotide triphosphates