answers to chapter 4 - garland · pdf file2 introduction to bioorganic chemistry and chemical...

Introduction to Bioorganic Chemistry and Chemical Biology 1

Answers to Chapter 4(in-text & asterisked problems)

Answer 4.1

The bulky tert-butyl group has a strong equatorial preference, the following two conformations will be predominant. The anti isomer cannot hydrolyze through neighboring group participation; the syn isomer can hydrolyze through neighboring group participation.

Answer 4.2

There are two plausible mechanisms that avoid expulsion of an anionic H2N– group. Without some mechanistic data, you cannot predict which is the most likely.

Answer 4.3

Introduction to Bioorganic Chemistry and Chemical Biology | A4096Van Vranken & Weiss | 978-0-8153-4214-4 © www.garlandscience.com design by www.blink.biz

O -

P-O

OO

OCH3

- O

P-O

OO

OCH3

:

..

anti syn


NN

O -R

NH2HO

NN

O -R

NH3+- O

.. BH

..

NN

O -R

NH2OHB:

NN

O -R

NH2- O

..

.. BHNN

OR

NH2HO-:

NN

O -R

NH3+OHB:

NN

OR

O -

BH

:

NNH

OR

O


5'3'5'

3'CGAUGCCGCGAGG

GUC5'3'C

GCG

UA

GC

UAGA

CCCU AGGGUC

GACC

CU

5'3'CGAUGCCGCG 5'

3'CGC

GUA

GC

UA

"kissing complex"stem loops

2 Introduction to Bioorganic Chemistry and Chemical Biology: ANsWers To CHApTer 4

Answer 4.4

The following figure shows the minimum free-energy structure from rNAfold and GeneBee and the second-lowest energy structure from MC-fold (the lowest-energy structure from MC-fold did not match).

Answer 4.5

Answer 4.6


C GAUGCCG

UG

GUUGA A

AU

CG CGCGGCAU CGCG

A

AUGCCGCGGCUA

GUCAAAA

G

GU

UCUGG

CC

GG

CG

C

CUUA

UU

G

ACCA

5'

3'


N

N

NNNNNN

N

N

NN

NNNNNN

NN

5'

3'

four types of base pairs: A•T, C•G, G•C, or T•A

four types of unpaired bases: A, C, G, or T

Total possibilities = 47• 44• 12 = 411• 12 = 50,331,648

twelve types of mis-matches:A•A, A•C, A•G, C•A, C•C, C•T, G•A, G•G, G•T, T•C, T•G, T•T


N

OO O

CH3

O -RNA

..

B: N

OO

O

CH3

ORNA

..-

N

OO

O

CH3

ORNA

..

H B

N

OO

O

CH3

ORNA

..-

-

H

+ NO

CH3

ORNA

H

ORNA

H

Introduction to Bioorganic Chemistry and Chemical Biology: ANsWers To CHApTer 4 3

Answer 4.7

Answer 4.8

Triphosphates are highly susceptible to nucleophilic attack, particularly in the presence of Mg2+ ions (not shown). The 2ʹ-hydroxyl group of a 3ʹ-nucleotidyl triphosphate would cyclize to give an unstable cyclic 2ʹ,3ʹ-phosphate.

Answer 4.9

There are two possible hybrid pairs: the DNA-binding domain–Ms2 and the activation domain–iron regulatory protein (as shown) or DNA-binding domain–iron regulatory protein and activation domain–Ms2 (not shown).


O

O

Ade

O

HOOP

O-O

Ura

3'

O

O

Ade

OOP

O-O

Ura

5'

3'

OMg

OP

O

POP

O- OO O

OO

OO

HO

CytMg ..

+

-

OP

OPO

O- O

O

MgO

HO

CytOP

O

O

O

-

O

HOOP

O-O

Cyt

O

O

Ade

O

OOP

O-O

Ura

3'OP

OPO

O- O

O

Mg

O-

O

O

Gua

OPO

-O

OH

OH

OH

O

Cyt

Thy

Ade

Gua

OH

OH

OH

OH

OH

OH

O

O

Gua

OPO

-O

OHO

5' O

O

Gua

OPO

-O

OHO

Cyt

Thy

Ade

Gua

OH

Cyt

Thy

Ade

Gua

leaving group

RNA Pol

templatestrand

templatestrand

templatestrand


O

O

CytHO

OP

OP

- O OP

- OO

O

- OO

OH

H.

O

O

CytHO

O. PO O - OH

P- O O

P

O

- OO

OH


GAL4DNA-binding

domains

iron regulatoryprotein

RNA library

MS2 viralcoat protein

transcription


Answer 4.10

Answer 4.11

The two lone pairs around the sulfur of the thioether are diastereotopic, as shown in the following structure. The enzyme is selective for one of these lone pairs, generating the diastereomer of sAM with a configurationally stable S configuration at sulfur. The reaction with methyl iodide reacts with both lone pairs at approximately equal rates, leading to a mixture of R and S sulfonium ions. The natural S diastereomer of sAM is a good substrate for methyltransferases, whereas the R diastereomer is not.

Answer 4.12

The phosphate indicated with the arrow still has an adjacent 2ʹ-oH group, whereas the other two phosphate diesters lack the adjacent 2ʹ-oH group. This 2ʹ-oH group can play a key role in mediating rNA cleavage, as discussed earlier in the chapter.


NH

O H

NH

O.

NH

O

.

NH

O

.

HN

O

.NH

O HN

OH

H

O O. .

OH.

NH

O HN

OH

O OH.

.

NH

O HN

O


S

O

HO OH

N

NN

N

NH2

+H3N

-O2C

: :

S

O

HO OH

N

NN

N

NH2

+H3N

-O2C

H3C

:

(S)-configuration

SAM


OO

O

BO

OO

O

Ade

OPO

- O

PO

- OO

PO

O -

n-..

this P–O bond iscleaved by exposure to base

lariat


Answer 4.13

Answer 4.14

Answer 4.15

Answer 4.16

ATG GGC CGC CGC CCC GCC CGT TGT TAC CGG TAT TGT AAG AACAUG GGC CGC CGC CCC GCC CGU UGU UAC CGG UAU UGU AAG AACMet Gly Arg Arg Pro Ala Arg Cys Tyr Arg Tyr Cys Lys Asn

(The three-letter abbreviations used here correspond to the first three letters of the amino acid, with the exception of asparagine and glutamine, which are abbreviated Asn and Gln to avoid confusion with aspartic acid and glutamic acid, respectively.)

Answer 4.17

so the number of possiple hexapeptides coded by these sequences is 26 = 64.


5'-GATCCGCACCGAGTTCAAGAACACCTTTTCAAGAGAGGTGTTCTTGAACTCGGTGTTCTTTTTTTCTAGAG-3'

CACCGAGUUCAAGAACACCGUGGCUCAAGUUCUUGUGG

UU UUAAGAGA3'-GAGAUCUUUUUUUCUU

5'-GAUCCG

transcription

sense

antisense


N

N

NH

H

N

N

A2451

NN

O

NN G2447

N HH O P

OO

OA2450

3

1

H

N

N

NH

N

N

A2451

NN

O

NN G2447

NH O P

OO

OA2450

H

H

H.. ..3

1

:


Gua

N

N

N

NHN

O

R

H

H

HH

O N N

NCyt

H

ManQ

N

N

N

N

N

OH

R

H

H

H

N O

N

O

Ura

wobblebase pair

Watson–Crickbase pair


G TAC G TGC CAGC

AGCT G T-C

T-G AAC5' 3'

Alaor

Glu

ThrorAla

AsporAla

GlyorAla

Alaor

Pro

Alaor Val


Answer 4.18

The Zn2+ ion acts a Lewis acid, coordinating to both the formamide carbonyl and the hydroxide nucleophile. The Zn2+ ion activates the carbonyl group toward attack and brings the hydroxide nucleophile into proximity with the carbonyl carbon.

Answer 4.19

B The enzyme lowers the entropic barrier by bringing the reactive carbon of NADH into close proximity with the diphthamide residue. Carbocation formation is the rate-determining step in an sN1 reaction. The enzyme probably lowers the en-thalpic barrier to ionization by stabilizing the oxocarbenium ion.

Answer 4.20

Because chloramphenicol disrupts all protein translation, chloramphenicol will prevent the cells from expressing the plasmid-encoded protein (chloramphenicol acetyl transferase) that confers resistance. Allowing the cells to grow before exposure to chloramphenicol ensures an adequate supply of the proteins that confer resistance.

Answer 4.21

Number of 50-mer rNAs = 450 = 1.3 × 1030

Molecular mass of a 50-mer DNA = 50 × 305 g mol–1 = 15,250 g mol–1

500 × 10–6 g × 1 mol/15,250 g × 6.02 × 1023 molecules mol–1 = 1.9 × 1017

1.9 × 1017/1.3 × 1030 = 1.6 × 10–13 (!)

*Answer 4.22

A 3ʹ-CATAGCTGTCCTCCT-5ʹ 5ʹ-GUAUCGACAGGAGGA-3ʹB 3ʹ-CATGGTGGT-5ʹ 5ʹ-GUACCACCA-3ʹ

Answer 4.23


NH

HN

O

S

H N

OO

OZn +

:HONHR

-HN

ONH

N

OHO

OO

Zn+

- ~~

peptidedeformylase

activesite

peptidedeformylase

activesite

actinoin protein/peptide

hydroxide anion


ON

H2NOC

OHHO

NAD+

NH

N

H2NOC

Me3N+

NHNH

O

O

:

EF-2

:: O

OHHO

+

O

HO

HO

NH

N+

H2NOC

Me3N+

NHNH

O

O

:+

oxocarbenium ionA


CU

C

G

GAG

GA

GCUC

CC

GUC

UG

CGG

CAG

GA

GGGA

GC

CCUCC

UA

GU

GCGG C

G

UGCC

GGA CCUA

GC

UA

GC

5'

5'3'

B*A 3'


Answer 4.24

*Answer 4.25

*Answer 4.28

Note that the presence of start and stop codons confirms that the reading frame is correct.

*Answer 4.31

Most amine-containing buffers are tertiary trialkylamines that can form stable adducts through acylation or sulfonylation. Tris is a primaryl alkylamine that can react readily with DepC to form stable carbamates.


OP

O

O ONa 1 M NaOH

H2O100 °C

*A

OP

O

O ONaOH

1 M NaOH

H2O100 °C

*B

OH

OH

O

O

Ura

O

O

HO

Ade

OPO

NaO

OH

PO

NaO(excess)

1 M NaOH

H2O100 °C

C

OP

ONa

O ONaHO

NaOP

O

O ONaOHOH

OH

O

HO

Ura

O

ONaP

ONaO

OH

ONaO

HO

Ade

OPO

NaO+

+

+


3'-CCGCUGGCUGGCA-5'5'-GGCGACC ACCGU-3'

CUGAUGAGG

CCGAAAGGCCG

AA

3'-CGCGUCGCUGCCG-5'5'-GCGCAGC ACGGC-3'

CUGAUGAGG

CCGAAAGGCCG

AA

A B

substrate

ribozyme

substrate

ribozyme


1 gaauuccgcu aaaccaaucu aucaaguccu gauuaaucug gugagcAUGG AGCUUUGUUG 61 GCUCACAACC AUCCAUGGUU CUUGAagaag cuuggagaga aaggggugug agaggagagg121 gugcucacuc cucacacucc cucacuuaaa acaguuuguu uuggcuuagc uuuggcuucu181 cugaucaaca agggaugugu ucuaacauuc uuucuugagu ggcggaagca gauacacauu241 cuccgacgga ggagaggcuu ggcuacagcc uggcaaaccg gcaagucaca aaaaaggcaa301 uggacuccau uggggucucu auggcuaugu agugcucaug uaguucuucu ugcuguagaa361 uguaauaaua aacaaaguug gucuuccuuu ugagaaguua ccagcuuuug cuguccaaaa421 uuacucaauu ugcagcugac uagaauuccu uucucucuuc aguuucugca gaugaguagg481 uaggcaauuu gugaucacuc ccuucccuuu ucaugucuuc uguguucccu uuuccaugcu541 uguuuguguu guuaguuaug accuuaugag gaaauaaaag aauaguacaa uucuaguccc601 ucaguuuagg auuguauucu auugaacuuu auuagaaaag uuuccagagu ccuuucuaaa661 aaaaaaaaaa aaaaaaaaa

AUGGAGCUUUGUUGGCUCACAACCAUCCAUGGUUCUUGAMetGluLeuCysTrpLeuThrThrIleHisGlySerSTOP

AUGGUUCUUGAagaagcuuggagagaaaggggugugagaggagagggugcucacuccucacacucccucacuuaa

MetValLeuGluGluAlaTrpArgGluArgGlyValArgGlyGluGlyAlaHisSerSerHisSerLeuThrSTOP

ACCESSION X69154; Glycine max ENOD40-1 mRNA.

Peptide A (highlighted)

Peptide B (underlined)


NH2

O

OEtO OEt

O.. +

HO

HO

OHTris

NH

HO

HO

OH

OEt

OpH 8

answers to chapter 4 - garland · pdf file2 introduction to bioorganic chemistry and chemical...

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