Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Principles of Drug Discovery > Drug discovery 6b > Flashcards

Drug discovery 6b Flashcards

0
Q

why is conformation of a drug important ?

A

it determines whether it will be a good drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

what bond angle is present in a tetrahedral shaped molecule ?

A

109.5 degrees

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what can all single covalent bonds do ?

A

spin

  • no effect for carbon-hydrogen bonds
  • when the central carbon- carbon bond in ethane spins the position of the hydrogen bonds change - this means you get different conformations of the molecule
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is newmans projection ?

A

projection looking down carbon carbon bond

- it is a way of defining rotation about a single bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what does the dihedral angle (torsion angle) permit ?

A

means you can define the conformation around that bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the conformation in ethane when the hydrogens at the back are maximally separated from those at the front ?

A

staggered conformation so the bond angle is 60 degrees

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the varying conformations of butane ?

A

when looking down the central carbons the methyl groups can be on the same side where the terminal methyl groups are closest= high energy state and they can be on opposite sides in which the termina methyl groups are furthest away from each other producing a low energy state
- also high energy when there is a clash between a terminal methyl and a terminal hydrogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the bond angle when the 2 bulk methyl groups in butane are maximally separated ?

A

180 degrees

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is the bond angle of butane in the anti and gauche state ?

A

anti- 180 degrees

gauche- 60 degrees

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what conformation does the butane molecule prefer to be in ?

A

prefers to be in one of the 3 lowest energy conformations anti or gauche

  • anti is sometime referred to as trans
  • this enables a choice of conformation for each single bond but also some restraint
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

in butane what can constrain conformational flexibility ?

A

constrained by adding in ring systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

why are there 2 isomers of butene ?

A

because it contains a double bond and therefore it cannot rotate
- cis and trans conformations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the bond angle when a nitrogen forms a quarternary ammonium ion ?

A

109.5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what conformational shape is cyclohexane ?

A

it is puckered and can form boat or chair conformation

- often an oxygen or nitrogen are inserted into this kind of puckered ring system e.g. glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

which conformation of cyclohexane is more stable ?

A

chair conformation is the most stable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

there are different conformations of acetylcholine so how did they determine which one was bioactive ?

A

achieved by restricting the conformation acetylcholine by inserting a cyclopropane ring into the middle of the molecule
- this resulted in analogues which mimic versions of acetylcholine that dont have a rotatable central carbon carbon bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is cyclopropane ?

A

its an odd molecule - triangle shape
ring system forces bonds angles to be 60 degrees which is a long way from the ideal 109.5
therefore it is rather unstable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

using cyclopropane to restrict acetylcholine into specific conformations enable the determination of the active form. which form was the active one ?

A

the trans version - only one of them - the active version was equivalent to a conformtion of ach with a 137 dihedral angle therefore not what we would consider to be the most stable conformation
cis isomers were inactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

when was the M2 muscarninc acetylcholine receptor x ray structure determined?

A

25/1/12

but the ligand to it was an antagonist- QNB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what do functional groups in organic compounds do ?

A

they form main interactions with drug target

impart certain properties to a compound

20
Q

what does the hydroxyl group in an organic compound do ?

A

does not ionise - doesnt form a hydroxide ion or release a proton
it can form hydrogen bonds

21
Q

what are organic compounds that contain a hydroxyl group called ?

A

alcohols

22
Q

what properties do hydroxyl groups have ?

A

they are polar and can form hydrogen bonds - therefore important for drug interactions

23
Q

what is an example of how hydroxyl groups form drug-target interactions ?

A

catechol hydroxyl groups of isoprenalin

24
Q

what is a carbonyl group ?

A

carbon with a double bond to an oxygen and then 2 single bonds to 2 other groups

25
Q

in a carbonyl group if the 2 single bonds to are to carbon atoms, what is produced ?

A

a ketone

26
Q

in a carbonyl group if one of the single bonds is to a hydrogen what is produced ?

A

an aldehyde

27
Q

in the carbonyl group what property does the carbon-oxygen double bond possess and what can it do ?

A

it is polar and it can accept a hydrogen bond

28
Q

what can the carboxyl group do ?

A

it can ionize

  • it releases a proton and is therefore an acid
  • the proton from the OH group can dissociate and form and negatively charged molecule- this is important as you may then be able to form electrostatic bonds
29
Q

what can amino/amine groups do ?t

A

they can bind protons

  • nitrogen atom becomes positively charged
  • when 4 protons are attached it forms a quarternary amine which is positively charged - this means the receptor is negatively charged
30
Q

in an amino/amine group, what can the lone pair on the nitrogen do ?

A

it can be shared with a proton to form a coordinated covalent bond - this causes the nitrogen to gain a positive charge

31
Q

what can the amide group do ?

A

it CANNOT ionize

but they are polar and can form hydrogen bonds

32
Q

describe the characteristics of the central carbon in an amide group :

A

it is trigonal planar

double bond is delocalised so that the carbon-nitrogen bond has some double bond character

33
Q

what are most drug targets ?

A

proteins

34
Q

what are proteins made up of ?

A

amino acids

backbone consisting of an amino group and a carboxyl group separated by a carbon - the alpha carbon

35
Q

how are the 20 naturally occuring amino acids distinguished?

A

distinguished by the nature of their side chain, the moiety attached to the alpha carbon

36
Q

what isomers are all the naturally occurring amino acids ?

A

L-isomers

37
Q

what are the different classes which the amino acids fall into ?

A 
no R 
sulphur
aliphatic 
aromatic
charged 
polar
tethered
38
Q

what amino acid has no side chain ?

A

glycine

39
Q

what amino acids are in the sulphur class?

A

cysteine

methionine

40
Q

what amino acids are in the aliphatic class?

A

alanine
valine
leucine
isoleucine

41
Q

what amino acids fall into the aromatic class ?

A

phenylalanine
tyrosine
trytophan
histidine

42
Q

what amino acids fall into the charged class ?

A 
aspartic acid 
glutamic acid 
arginine
lyseine 
histidine
43
Q

what amino acids fall into the polar class ?

A

serine
threonine
glutamine
asparagine

44
Q

what amino acid falls into the tethered class ?

A

proline

45
Q

how are amino acids linked together ?

A

by peptide bonds= covalent bonds
the end with the amino group= n terminus
end with the carboxylic acid group= c terminus
formation of the peptide bond results in amide

46
Q

why dont peptide bonds rotate ?

A

because it is an amide group
it has partial double bond character due to the delocalisation of the electrons
it is usually fixed in the trans conformation

47
Q

what shape are the amide groups ?

A

planar

48
Q

how are secondary structures and proteins folds produced in proteins ?

A

the peptide bonds cannot rotate so they confer little flexibility

it is the other bonds in the main chain that can rotate and produce secondary structure and protein folds
- like in butane there are 3 main conformations for each bond but the final conformation will depend on the global stability of the protein fold as a whole

Principles of Drug Discovery (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions