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week 19 (Y2) > the medicine > Flashcards

the medicine Flashcards

1
Q

prokaryotic ribosome size

A

30s

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2
Q

eukaryotic ribosome size

A

50s

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3
Q

what are ribosomes responsible for

A

protein synthesis

Without functional ribosomes, bacteria
cannot survive. This is why ribosomes are
such an important target for new
antibiotics

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4
Q

what are the 4 phases of bacterial protein synthesis

A
  1. Initiation
  2. Elongation (transpeptidation)
  3. Termination
  4. Ribosome recycling
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5
Q

describe initiation

A

Various initiation factors are involved.
* The small ribosomal subunit, typically bound to an
aminoacyl-tRNA containing the first amino acid methionine,
binds to an AUG codon on the mRNA and recruits the large
ribosomal subunit.
* The two subunits to clamp around the mRNA with the
initiator tRNA bound in the ribosomal P-site.

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6
Q

what do Oxazolidinones do?

A

inhibits initiation

inezolid is a synthetic oxazolidinone antimicrobial drug
* Indicated for gram-positive infections
* Linezolid binds to a site on the bacterial 50S subunit, preventing the formation
of a functional 70S initiation complex.
* Stops protein synthesis
* Linezolid is bacteriocidal against the majority of streptococcal strains and
bacteriostatic against staphylococci and enterococci.

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7
Q

what is transpeptidation, elongation

A

The amino acid at the P site is transferred to the amino acid
at the A site of the growing polypeptide chain
TRANSPEPTIDATION

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8
Q

describe movement of ribosome from site letters

A

EPA

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9
Q

describe elongation

A
  1. A new aminoacyl-tRNA to binds to the codon in the A site.
  2. The amino acid at the P site is transferred to the amino acid
    at the A site of the growing polypeptide chain -
    TRANSPEPTIDATION
  3. The two tRNA units remain bound to the mRNA and the
    ribosome moves along by one codon so that the two tRNA
    units now occupy the E and P sites.
    * The spent tRNA dissociates from the E site and the process
    is repeated.
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10
Q

when does the end of translation occur

A

The end of translation occurs
when the ribosome reaches one
or more STOP codons (UAA, UAG,
UGA).

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11
Q

describe inhibition with aminoglycosides

A

change the shape of 30s subunit
mis reading mRNA

bacteria lack proof reading mechanisms to deal with incorrect protein production

streptomycin
gentamycin

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12
Q

describe inhibition with tetracyclines

A

prevent amino acids from entering the ribosome at the 30s subunit

stalls protein synthesis

tetracyclines
minicyclin
doxycycline

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13
Q

eaxmples of tetracyclines

A

tetracyclines
minicyclin
doxycycline

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14
Q

exampes of aminoglycosides

A

streptomycin
gentamycin

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15
Q

how does streptomycin inibit protein synthesis

A

Streptomycin binds adjacent to the 30S decoding
site, forming hydrogen bonds and salt bridges with
backbone phosphates.
* Streptomycin distorts the ribosomal decoding site.
* Streptomycin preferentially stabilizes near-cognate
codon-anticodon interactions and thus induces
ribosomal misreading of the genetic code and
incorrect proteins are synthesised.

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16
Q

describe tetracycline structures

A

4 x 6-membered rings in a
linear arrangement
Phenol on left hand side

Natural products
Significant antimicrobial resistance

Semi-synthetic
Reserved for 2nd line treatment
when other drugs meet resistance.

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17
Q

describe 3rd generation, semisynthetic tetracyclines

A

Tigecycline
* Active against MRSA, VRE, many Gram negative
bacteria
* Efflux mechanisms of resistance can be a problem.

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18
Q

Properties and uses of tetracyclines

A

Orally absorbed
* Used to treat chest infections, acne, periodontal disease (and other non-
infection based conditions)
* Broad spectrum of activity: G+, G- bacteria, anthrax, Yersinia, Rickettsia
(typhus and Q fever), Chlamydia (trachoma, nonspecific urethritis),
mycoplasma, spirochaetes, Neisseria meningitidis.
* Doxycycline used in treating malaria
* Deposit in calcifying tissue (bone and teeth) causing staining, should not be
used in children under 8 yr or in pregnancy. Bone structure weakened.
* Good at binding metal ions – Ca2+, Zn2+, Fe3+, Al3+ [Why is this important?]
* OTHER EFFECTS! – anti-inflammatory

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19
Q

what is an example of inhibition of transpeptidation 1

A

Puromycin

Causes premature chain termination.
* Puromycin resembles the aminoacyl-tRNA
* It has an “NH” instead of the “O” that joins an amino acid
to tRNA
* The resulting stronger amide bond is not reactive enough
→ new peptide bond forms slowly.
* Ribosome stalls or incomplete protein chain is released.

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20
Q

what is an example of inhibition of transpeptidation 2

A

Chloramphenicol

Selective action on peptidyl transferase of the 50S subunit,
blocks the 50S ribosome, preventing peptide bond formation.

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21
Q

how any steroisomers are there of chloramphenicol

A

2 chiral centres

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22
Q

what is an example of inhibition of transpeptidation 3

A

Kanamycin

Kanamycin (an aminoglycoside) Causes misreading
of the code by interfering with the base pairing.

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23
Q

what is an example of inhibition of transpeptidation 4

A

Kirromycin

tRNA transfer is facilitated by 2 elongation factors

EF - Tu and EF - Ts

EF-Tu binds to GDP and GTP

GTP is hydrolysed and under goes a conformational change and dissociates

Kirromycin blocks this dissociation

Stalling protein synthesis

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24
Q

what is an example of inhibition of transpeptidation 5

A

Fusidic acid

Penetrates bone well, used in
staphylococcal osteomyelitis, also for
some MRSA infections
* Prevents translocation and EFG
dependent cleavage of GTP, also inhibits
80S EF2
* Does not enter mammalian cells.
* Inhibits the multiple-turnover EF-
G·GTPase. This stops ribosome
movement.

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25
Q

Inhibitors of Translocation 1

A

Macrolide Antibiotics

Macrolides bind to 50S ribosome and prevent movement from one codon to the
next, halting translation.
* Macrolides have a large ring system containing an ester linkage (in the ring)
* e.g. Erythromycin

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26
Q

eaxmples of inhibitors of termination

A

Inhibitors include Puromycin, streptogramins and some macrolides

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27
Q

ribosome structure

A

made up of two subunits
* The subunits lock around the messenger RNA and
then travel along the length of the messenger RNA
molecule reading each three-letter codon.
* The ribosome serves as a docking station for the
transfer RNA that matches the sequence of bases on
the messenger RNA.
* Each three-letter codon on the messenger RNA pairs
with the matching anticodon on a specific transfer
RNA, and that specific RNA allows for the addition of
a specific amino acid on the end of the growing
protein chain.
* When the ribosome encounters a stop codon, it falls
off the mRNA molecule and releases the protein for
use in the cell.

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28
Q

what is mRNA

A

Messenger RNA (mRNA) molecules carry the coding sequences for protein synthesis – “transcripts” -
dictates the order in which amino acids should be added to a growing protein as it is synthesised.

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29
Q

what is rRNA

A

Ribosomal RNA (rRNA) molecules form the core of a cell’s ribosomes

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30
Q

what is tRNA

A

Transfer RNA (tRNA) molecules carry activated amino acids to the ribosomes during protein synthesis

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31
Q

what is chloroquine

A

anti malarial agent

Chloroquine is used for the prophylaxis of malaria in areas
of the world where the risk of chloroquine-resistant
falciparum malaria is still low.

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32
Q

what is mefloquine

A

anti mlarial drug

Mefloquine is used for the prophylaxis of malaria in areas
of the world where there is a high risk of chloroquine-
resistant falciparum malaria

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33
Q

what is primaquine

A

antimalarial drug

Primaquine is used to eliminate the liver stages of P. vivax
or P. ovale following chloroquine treatment

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34
Q

what is proguanil

A

Proguanil is used (usually with chloroquine, but
occasionally alone) for the prophylaxis of malaria

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35
Q

what is pyrimethamine

A

Pyrimethamine should not be used alone, but is used with
sulfadoxine (in Fansidar)

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36
Q

describe the mechanism of chloroquine

A

Hemoglobin
(parasite metabolim)
Haem (Soluble & TOXIC!)
(bio-crystallisation)
Hemozoin (Insoluble non-toxic crystals)

chloroquite inhibits bio crystallisation

After passive diffusion, chloroquine becomes trapped in the
acidic parasitic digestive vacuole in the protonated form.
* Chloroquine caps hemozoin molecules to prevent further
biocrystallization of haem, → haem buildup.
* Chloroquine binds to haem to form a complex that is highly
toxic to the cell and disrupts membrane function.
* Toxic concentrations of haem and the complex → cell lysis
→ parasite cell autodigestion

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37
Q

what drugs intefere with the haem disposal mechanisms in
infected erythrocytes

A

Chloroquine, mefloquine, primaquine, quinine,
lumefantrine

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38
Q

what is proguanil

A

pro drug

produces cycloguanil
inhibits the parasites dihydrofolate reductase

it is thought that proguanil may act on another target also

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39
Q

what is the problem with proguanil

A

poor metabolism can decrease conversion of proguanil to cycloguanil in certain population african and asian

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40
Q

Pyrimethamine what does it do

A

It is a folic acid antagonist and inhibits the
dihydrofolate reductase of plasmodia → blocks
the biosynthesis of purines and pyrimidines.
* These are essential for DNA synthesis and cell
multiplication.

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41
Q

what does having a lot of chiral centres indicate

A

there will be an issue with synthesis

hard to synthesie

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42
Q

what is artemisinin

A

Artemisinin is a compound derived from the sweet wormwood plant (Artemisia annua). It is a potent antimalarial drug used to treat malaria, particularly strains that have developed resistance to other antimalarial medications. Artemisinin and its derivatives are often used in combination therapies to enhance their effectiveness and reduce the likelihood of resistance development. Artemisinin-based combination therapies (ACTs) are recommended by the World Health Organization (WHO) as a first-line treatment for uncomplicated malaria.

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43
Q

what are the other two analogues of artimisinin

A

artemether
artesunate

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44
Q

what is Artesunate

A

An injectable water-
soluble semi-synthetic
analogue

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45
Q

what is Artemether

A

A prodrug for
dihydroartemisinin
Artemether and
lumefantrine
combination therapy

Mechanism: interaction with heme, or ferrous ions, in the
parasite food vacuole → cytotoxic radical species.
* Artemether has a rapid onset of action and is rapidly cleared
from the body.

Lumefantrine has a much longer half life and is believed to
clear residual parasites

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46
Q

what is atovaquone

A

Highly lipophilic
* Acts by selectively affecting mitochondrial
electron transport and parallel processes
such as ATP and pyrimidine biosynthesis.
* Does not cause myelosuppression (important
for patients who have undergone bone
marrow transplantation)

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47
Q

what is Falciparum malaria

A

Falciparum malaria (malignant malaria) is caused by P.
falciparum. In most parts of the world P. falciparum is now
resistant to chloroquine which should not therefore be given
for treatment.

Drug treatment is by combination therapy, NOT monotherapy

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48
Q

what are Benign malarias

A

reccuring malarias

Chloroquine is the drug of choice for the treatment of
benign malarias (but resistance becoming widespread).

P. vivax and P. ovale
a radical cure (to
destroy parasites in the liver and thus prevent relapses)
is required.

This is achieved with primaquine

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48
Q

Prophylaxis against malaria
Protection against bites

A

Mosquito nets impregnated with permethrin
provide the most effective barrier protection against
insects; coils, mats and vaporised insecticides are also
useful

Diethyltoluamide (DEET)
n lotions, sprays or roll-on
formulations is safe and effective when applied to the
skin but the protective effect only lasts for a few hours.
Long sleeves and trousers worn after dusk also provide
protection.

49
Q

Global warming and its effect on mosquito range

A

As the world warms, the mosquito range moves northwards.
This could potentially expose many new populations to
mosquito-born diseases.

50
Q

what is Trypanosomiasis

A

Human African trypanosomiasis (sleeping sickness) is a
widespread tropical disease that can be fatal if not treated.
Spread by the bite of an infected tsetse fly.

affecting CNS

51
Q

Trypanosomiasis treatment

A

Pentamidine, Berenil, Eflornithine for prophylaxis and
treatment

Tryparsamide and Melarsoprol toxic arsenic compounds
needed in advanced cases

52
Q

what is Suramin

A

For first stage treatment
of Trypanosoma brucei
rhodesiense sleeping
sickness

53
Q

why is sumarin used parenterally

A

it has very poor oral bio abvailibility

54
Q

Trypanosomiasis – symptoms

A

The bite erupts into a red sore and within a few weeks
the person can experience fever, swollen lymph glands,
aching muscles and joints, headaches and irritability.
* In advanced stages, the disease attacks the central
nervous system (crosses the BBB), causing changes in
personality, alteration of the biological clock, confusion,
slurred speech, seizures, and difficulty walking and
talking. If not treated, the person will die.

55
Q

Stage 1: in subcutaneous tissues, blood and lymph, treatment

A

The drugs used in the first stage of the disease are of lower
toxicity and easier to administer. The earlier the disease is
identified, the better the prospect of a cure.

56
Q

Stage 2: the parasites cross the blood-brain barrier to infect
the central nervous system, treatment

A

Second stage drugs have to cross the blood-brain barrier to
reach the parasite. Such drugs are toxic and complicated to
administer.

57
Q

what is Pentamidine

A

For first stage treatment of Trypanosoma brucei gambiense
sleeping sickness
* Despite its undesirable effects (which include liver or
kidney dysfunction, hypertension, hypotension,
hypoglycemia, hypocalemia, leukopenia, thrombcytopenia,
anemia, and allergic reaction), it is in general well tolerated
by patients. (!)
* It is thought that the drug interferes with nuclear
metabolism producing inhibition of the synthesis of DNA,
RNA, phospholipids, and proteins.

58
Q

what is Melarsoprol

A

Second stage treatment
for both forms of infection

Crosses the blood-brain barrier
* It is derived from arsenic and has many undesirable side
effects: cutaneous reactions, polyneuropathy, diarrhoea and
fever and reactive encephalopathy (encephalopathic
syndrome) which can be fatal (3% to 10%).
* An increase in resistance to the drug has been observed in
several foci particularly in central Africa.

59
Q

what is Eflornithine

A

Second stage treatment but
only for T. gambiense

Less toxic than melarsoprol
* Crosses the blood-brain barrier
* The regimen is strict and difficult to apply.
* A combination treatment of nifurtimox and eflornithine
introduced in 2009.

60
Q

what is the mechanism of action of Eflornithine

A

Enzyme-activated, irreversible inhibitor of ornithine
decarboxylase (ODC), the key enzyme in the conversion of
ornithine to polyamines.

Polyamines are essential for nucleic acid and protein
synthesis in protozoa.

61
Q

what catalyses the change in the mechanism of action

A

Di floro mthyl group,

62
Q

what is Leishmaniasis

A

sand fly vector

Leishmania tropica and Leishmania donovani cause cutaneous
(Baghdad boil, Dehli sore, oriental sore, Kala-azar, chiclero
disease) and visceral infection (liver and spleen).

63
Q

Leishmaniasis agents

A

Pentamidine, amphotericin, antimony compounds
(sodium stibogluconate)

64
Q

what is Amphotericin B

A

A polyene antibiotic
* second line of treatment for visceral leishmaniasis

use restricted by its acute toxicity, low therapeutic index
and the need for parenteral administration.

65
Q

what is Sodium Stibogluconate

A

The mechanism of action is possibly something to do
with a reduction in ATP and GTP synthesis leading to
decreased macromolecular synthesis.

Leishmaniasis treatment

66
Q

what is Chagas’ disease

A

Trypanosoma cruzi transmitted by bites to face by
reduviid bug (Mexico, South America).
* Invades heart muscle (sudden heart failure)
* damages nerves in GI tract (mega colon).

67
Q

treatment agents for Chagas’ disease

A

Nifurtimox and Benznidazole

68
Q

similaries between Nifurtimox and Benznidazole

A

The nitro group of both drugs is reduced to an amino group
by the action of nitroreductases, with the formation of
various free radical intermediates and electrophilic
metabolites

69
Q

mechanism of Nifurtimox

A

intracellular reduction → nitro radical followed
by redox cycling, and production of O2− and H2O2 is the
main mechanism of action of against T. cruzi.

70
Q

mechanism of Benznidazole

A

It is likely that the reduced metabolites of
benznidazole are involved in its trypanocidal effects by
covalent bonding to macromolecules.

71
Q

what is Amoebiasis

A

Entamoeba histolytica
* lives in the gut (harmless cyst form)
* can invade gut mucosa (amoebic dysentery)
* secondary spread (liver abscesses)

72
Q

agents for amoebiases

A

Metronidazole, tinidazole and diloxanide

73
Q

what is Metronidazole

A

Enters the cell as a prodrug by passive diffusion and is
activated by reduction of the nitro group in specific
organelles in the protozoa.
* The activated forms are cytotoxic and can interact with the
DNA molecule → inhibition of DNA synthesis and DNA
damage by oxidation → single-strand and double-strand
breaks → DNA degradation and cell death.

74
Q

what are the two possible genotoxic pathways for nitro group reduction

A

anerobic and aerobic

75
Q

describe the anerobic pathway for nitro group reduction

A

formation of the nitro redical anion

further reduction occurs via the formation of nitroso and hydroxylamin derivatives

ultimate products are the primary amines

hydroxyl radicals could induce single and double strand breaks

hydroxyl amino acid groups could form DNA adducts

76
Q

describe the aerobic pathway for nitro group reduction

A

formation of the nitro redical anion

radical is rapidly oxidised by O2

produces superoxide and hydroxide radical anions.

77
Q

what is Tinidazole

A

A synthetic antiprotozoal agent
similar to metronidazole

It is
suggested that the toxic free radicals covalently bind to
DNA → DNA damage → to cell death.

78
Q

what is Diloxanide [furoate]

A

An anti-protozoal drug used in the treatment of
Entamoeba histolytica and some other protozoal
infections.
* Mechanism unknown - may inhibit protein
synthesis
* Destroys the trophozoites of E. histolytica that
eventually form into cysts. The cysts are then
excreted by persons infected with asymptomatic
amebiasis.
* Diloxanide furoate is a prodrug and is hydrolysed
in the gastrointestinal tract to produce diloxanide,
the active ingredient.

79
Q

what is Giardiasis

A

Giardia lamblia lives in gut, does not invade tissues,
* Causes chronic diarrhoea

80
Q

agents for giardiasis

A

Metronidazole, tinidazole, mepacrine

81
Q

what is Mepacrine (Quinacrine)

A

Exact antiparasitic mechanism
unknown
* Binds to DNA in vitro by intercalation
between adjacent base pairs,
inhibiting transcription and translation
to ribonucleic acid (RNA).

Mepacrine (Quinacrine)
* Does not appear to localize to the nucleus of Giaridia
trophozoites, suggesting that DNA binding may not be
the primary mechanism.

82
Q

what is Trichomoniasis

A

Trichomonas vaginalis present in the urogenital
system, sexually transmitted, vaginitis

83
Q

agents Trichomoniasis

A

Agents: Metronidazole, tinidazole

84
Q

what is Pneumocystis carinii pneumonia (PCP)

A

Pneumocystis carinii present in lungs as cyst form.
* HIV infection leads to activation of organism and fatal
pneumonia.

85
Q

agents for Pneumocystis carinii pneumonia (PCP)

A

Pentamidine, trimethoprim, sulphonamides,
atovaquone and trimetrexate

86
Q

what is Trimethoprim

A

Trimethoprim is a pyrimidine analogue that inhibits DHFR
and disrupts folate synthesis (an essential part of the
thymidine synthesis pathway) → starves the organism of
nucleotides necessary for DNA replication.

87
Q

what is Trimetrexate

A

Trimetrexate is a competitive inhibitor of protozoan DHFR.

88
Q

what is Toxoplasmosis

A

Toxoplasma gondii transmitted from cat faeces, lamb,
beef. Causes glandular fever-like condition, severe
consequences in first trimester of pregnancy (effects on
foetus).

89
Q

agents for Toxoplasmosis

A

Agents: Pyrimethamine, sulphonamides, clindamycin,
* clarithromycin, azithromycin (used in new-born
prophylaxis of eye infections)

90
Q

what is Clarithromycin

A

Clarithromycin is first
metabolized to 14-OH
clarithromycin, which is active
and works synergistically with its
parent compound

Like other macrolides, it then penetrates bacteria cell wall
and reversibly binds to domain V of the 23S ribosomal
RNA of the 50S subunit of the bacterial ribosome,
blocking translocation of aminoacyl transfer-RNA and
polypeptide synthesis.

91
Q

what is clindamycin

A

ClindamycinAzithromycin, a semisynthetic
antibiotic belonging to the
macrolide subgroup of azalides

92
Q

what is Azithromycin

A

Azithromycin, a semisynthetic
antibiotic belonging to the
macrolide subgroup of azalides

93
Q

what is Cryptosporidiosis

A

Cryptosporidium parvum present in water contaminated with
animal faeces.
* Invades and reproduces in epithelial cells of small intestine.
* Causes severe diarrhoea

common in HIV

94
Q

agents for Cryptosporidiosis

A

No routine treatment available, macrolide spiramycin
used in HIV

95
Q

what is Spiramycin

A

A 16-membered macrolide
* Inhibits translocation by
binding to bacterial 50S
ribosomal subunits.
* Potent inhibitor of the
binding to the ribosome of
both donor and acceptor
substrates. Spiramycin
induces rapid breakdown of
polyribosomes.

96
Q

tell me about metrondiazole as an antibacterial agent

A

Metronidazole is an antibacterial and antiprotozoal medication used to treat a variety of infections caused by certain bacteria and parasites

97
Q

tell me about metrondiazole MOA

A

enters cell as prodrug
via passive diffusion
activated by redution of nitro group
in specific organelles in proteoza

activated forms are cytotoxic
can interact with DNA
inhibits DNA synthesis and causes damage
via oxidation

single and double strand breaks
DNA degredation and cell death

98
Q

tell me about nitrofuratonin similar MOA to metrondiazole

A

used for UTIs

99
Q

tell me about rifampin

A

semisynthetic antibiotic

obtained by reacting 3-formylrifamycin and 1-amino-4-methylpiperazine

100
Q

tell me about MOA of rifampin

A

inhibits bacterial RNA polymerase (responsible for RNA transcription) by forming a stable drug-enzyme complex

mammalian enzumes are not effected ny rifampin

bacterial resistance yo rifampin is caused by mutations leading to a change in the structure of the beta subunit of RNA polymerase

101
Q

what does DNA helicase do

A

promotes strand seperation at the replication fork

102
Q

what does DNA polymerase III do?

A

primary enzyme of replication, attaches nucelotides to the growing DNA chain and proof reads.

103
Q

what does DNA polymerase I do?

A

fills in gaps on lagging strand and removes RNA primers

104
Q

what is primase

A

makes short RNA primers for the lagging strand

105
Q

what do topoisomersases I do?

A

relax supercoiled DNA

106
Q

what do topoisomerases II do?

A

DNA gyrase, promotes negative supercoiling and maintains the shape of the chromosome

introducing double-strand breaks

107
Q

what do topoisomerases III do?

A

removes negaive supercoiling

Resolves DNA knots and catenanes by introducing double-strand breaks and passing DNA duplexes through each othe

108
Q

what topoisomeraes IV do?

A

removes knots and links behind replication fork

introducing transient double-strand breaks and passing one DNA duplex through another,

109
Q

how do quinolones inhibit DNA

A

inhibit DNA gyrase

block re sealing of bacterial DNA strands on supercoiling

causign bacterial chomosomes to break into multiple fragments

quinolones are 100 X more active against bacterial vs human gyrases

110
Q

what is antigene oglonucleotides

A

antigene stratigies require triple forming oglionucleotides TFOs

these form triple helical structures with duplex DNA targets

Antigene oligonucleotides in TFOs are synthetic DNA or RNA molecules designed to bind to specific DNA sequences within a gene’s promoter region. By binding to these sequences, they interfere with the binding of transcription factors or RNA polymerase, ultimately inhibiting gene expression.

111
Q

purine bases targeting

A

targeting achievable by 2 hoogsteen hydrogen bonds

111
Q

what is Tm

A

the melting temp

the temp at which 50% of dissociation of triple helix into TFO and double helix or dissociation of double helix int single strandec coil

112
Q

pyrimidine bases targetting

A

targeting achievable by 1 hoogsteen hydrigen bond

113
Q

what is TFO design limited to

A

limited to polypurine targets unlike antisense ddesign

114
Q

tell me about hoogsteen paired TFOs

A

pyrimidine TFOs form isomorphous triplex structures

there is a need for protonation of cytosine N3 imparts pH instablity

replacement of H by CH3 at C5 is stabilising but only marginally

115
Q

tell me about pH independed G,A containing TFOs

A

they form stable triplexes over a wide pH range esp 7.2

GGA and AAT triplexes are not isomorphous , they still need improving

umodified DNA backbone is easily hydrolysed in vivi, therefore a short half life

116
Q

targeting DNA gyrase in E.coli

A

stable at pH 7.2
Tm vale is 30 degrees celcius

bacterial growth is inhibited by the prescence of TFOs vs abscence control

TFO is bacteroistatic wheras fluroquinolones are bacteriocidal

117
Q

tell me about TFO backbones

A

LNA monomers are comercially available
LNA resists enzymatic hydrolysis so there is a longer half life, in vivo
LNA is more A-DNA and RNA like in conformation
all LNA backbone oglios suffer from self pairing
typical solution to self pairing is to form chimeric oligos

118
Q

what is an LNA

A

locked nuclaic acid

119
Q
A

week 19 (Y2) (3 decks)

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