Methods in Drug Discovery 2

Question 1

what is rational design

Answer 1

a powerful strategy but with certain perquisites that can be used to help work towards synthesizing a drug

Question 2

what does rational design require

Answer 2

structural data which can often be hard to obtain

Question 3

what are the 3 forms of screening

Answer 3

extensive
random
high throughput

Question 4

what is extensive screening

Answer 4

a new chemical entity being screened against a variety of biological targets. this type is often done to new classes of compounds.

Question 5

what is random screening

Answer 5

therapeutic objective is fixed with thousands of compounds tested against a small number of screens without regard to the structure of the compounds under test

Question 6

what is high throughput screening

Answer 6

the combination of random + extensive through the use of robots

Question 7

what is combinatorial chemistry

Answer 7

prepare molecules in every combination in the same reaction pot

Question 8

what is the limitation of combinatorial chemistry

Answer 8

compounds produced have limited structural diversity

Question 9

in practice what form are combinatorial libraries made from

Answer 9

solid bead known as polymer support

Question 10

What are the main advantages of combinatorial chemistry

Answer 10

different starting materials and products can be linked to separate beads meaning that all the beads can be exposed to the same reagent at the same time.

starting materials and products are bound to a solid support, excess reagents or unbound by products can easily be removed by washing the resin which means excess reagents can be used

Intermediates in a reaction sequence are bound to the bead and do not need to be purified

Question 11

how are the separated supports identified

Answer 11

by a series of deconvolution techniques such as liquid chromatogrpahy mass spectrometry

Question 12

how can the combinatorial mixtures be seperated

Answer 12

high performance liquid chromatography

Question 13

what are the two approaches to drug discovery

Answer 13

we have a molecule and want to find out what it can target

we have a target and want to find a molecule to bind it

Question 14

what is a molecule

Answer 14

a collection of functional groups which are connected together

Question 15

what must a molecule have for drug target binding

Answer 15

correct groups

correct position

Question 16

what is fragment based drug discovery

Answer 16

use of a structural method to find out how fragments bind

which gives greater acess to chemical space and links rational design with high throughput screening

Question 17

what defines a fragment

Answer 17

8 - 18 non hydrogen atoms

follows the rule of 3

mass of <300
hydrogen bond donors <3
hydrogen bond acceptors <3
clogP = 3
number of rotatable bonds <3

Question 18

what are the pros of fragment based drug discovery

Answer 18

systematic approach

gives access to a far larger section of chemical space than other methods

rapid via high throughput methods

combines rational design with high throughput approach

Question 19

what are the cons of fragment based drug discovery

Answer 19

requires structural information

needs access to high tech techniques