lect 2

Question 1

Biological molecules are modular b/c

Answer 1

• b/c they can easily assemble and disassemble for reuse complex structures
  only 1 enzyme is need for each biomolecular type and function listed below
  o Shape and density determine binding (noncovalent interactions—ionicdissociation//>solubility in a 3D way for a drug and biomolecule)
   Can be covalent after bonding

Question 2

proteins are…

Answer 2

linear chain of amino acids held by amide bonds
o Made by ribosome
o Disassemble by proteasome
o Drug comes into effect by binding to bio molecules
 Drug binds to substrate modification response (universal)

Question 3

nucleic acids are…

Answer 3

linear chain of nucleotides held by phosphate esters

Question 4

polysaccharides are…

Answer 4

linear chains of sugars, some are branched and held by acetals

Question 5

lipids are…

Answer 5

linear chains of acetate or propionate whose assembly units are hidden held by aldol

Question 6

how do proteins differ from each other and how are they the same

Answer 6

• 20 AA that have the same backbone and stereochemistry (R groups are hashed)
  o Differ from their side chains ‘R’
  o Special AA: glycine and proline—no side chain, affects rotation)

Question 7

Primary structure of Proteins

Answer 7

• Seq of AA from n terminus (nitrogen) to c terminus (carboxylic)

Question 8

Secondary structure of Proteins

Answer 8

• Local order in the backbone
• Helix
  o Ribbon
  o H bonding b/w peptide bonds
• Beta strand
  o Same plane, flat paper=sheet
   Strands can associate together
   Large sheets curl around themselves forming cylinders= BARREL
   H bonds hold sheet together
   Parallel or antiparallel

Question 9

• Loops

Answer 9

o No defined secondary structure
o Spaghetti on ribbon diagrams

Question 10

• Turns

Answer 10

o Chain changes direction by a large amount
o Connect secondary structure elements

Question 11

how does Conformational and chiral centres restrict rotations in amide bonds (amide and alpha carbon)

Answer 11

o Intermolecular forces acting intramolecularly causing structure to fold
o Amide chooses s-trans b/c its more stable—no steric interference
o Side chains—hydrogen bonding with backbones, nonpolar side interact with other nonpolar chains= folding

Question 12

tertiary structures

Answer 12

• Overall 3D shape of protein = secondary structures combined
• Nonadjacent regions interact
  o AA side chains
  o 2 secondary structures
   Causes secondary structures to fall back on themselves
   Noncovalent bonds

Question 13

quaternary structure

Answer 13

• 2+ proteins bind together e.g. Hb
• Subunits can be same or diff
• Protein-protein interactions
  o Strong
  o Chem rxns
  o Surface area
  o Expulsion of water
  o They stick tightly

Question 14

attraction forces in tertiary structures

Answer 14

o Disulfide covalent bond b/w AA
o Ionic bonding
o Hydrogen bonding
o Van der Waals
 Polar side chains outside of protein
 Nonpolar inside of protein
* Holds protein together
* Dipoles and H bonding weaker in water but are stronger in nonpolar environment
o Protein dissociates in water but remains in nonpolar environ slide41

Question 15

protein shape

Answer 15

Structure=function
* Most of the protein is a scaffold to hold everything together in the correct shape
* Small part is functional

Question 16

protein target for drugs

Answer 16

enzymes
receptors
ion channels
structural proteins

Question 17

enzymes

Answer 17

o Drug stop enzymes from working

Question 18

receptors

Answer 18

o Activate (agonist) deactivate (antagonist) the receptor
o May do both

Question 19

ion channel

Answer 19

o Open/close the channel

Question 20

structural protein

Answer 20

o Interfere with assembly/disassembly of protein structures

Question 21

enzymes catalyze rxns by

Answer 21

providing a designed environment for the transition state of a reaction
o Enzymes bind tightly to transition states (dec in activation energy)
o Enzyme trans state  product (reversible)
* Enzyme active site is small the rest is for support
* Active site chemistry is complimentary to trans state
* Enzyme binds to substrate
o Both change shape to get an induced fit
o Substrate is converted into product and is released (change in shape)
 Can be done by lock and key (sub. Is exact shape as enzyme)
 Induced fit (conform. Change activates and deactivates enzyme)

Question 22

inhibitions

Answer 22

competitive, non competitive, uncompetitive, irreversible

Question 23

competiive

Answer 23

o Inhibitor fights w/ substrate for active site
o Disulfiram (Antabuse)
 Blocks acetaldehyde dehydrogenase and produces a hangover
at 1 but steeper

Question 24

noncompetitive

Answer 24

o Inhibitor binds elsewhere from the active site
 Prevents trans state from forming since it alters the shape of the enzyme
o Substrate binds to active site
o fluconazole
no longer at 1 and steep

Question 25

uncompetiive

Answer 25

o Inhibitor binds to trans state
 Destroys catalytic ability of trans state
 Lithium
not at 1 but parallel to slope at 1 b/c equilibrium of ES and I

Question 26

irreverisble

Answer 26

o Covalent inhibitors
o Bond covalently to enzyme active site
o Alt conformations or disabling f’nal groups
o Bond on active site
o Penicillin

Question 27

recpetors binding…

Answer 27

o Chem interactions b/w messenger (ligand) and receptor, changes shape of receptor
o Conformational change allows 2nd messenger to bind or release
 Agonist binding allows shape change that result in a signal
 Bind at active site as messenger
 Some agonists bind at diff locations (allosteric sites)

Question 28

receptors catalysis

Answer 28

o Chem interactions b/w messenger (ligand) and receptor, changes shape of receptor
o Shape change allows the creation or destruction of catalytic function

Question 29

agonist stimulate messenger

Answer 29

• Agonists activate receptor and replaces messenger; binding induces shape change that results in transmission of a signal
  o Bind at same location
  o Some bind at other sites (allosteric)
  o Asthma drugs are adrenaline agonist
   Adrenaline receptors in lungs stimulate bronchial opening when activated
   Bind to active site of noradrenaline receptor

Question 30

alloesteric modulators

Answer 30

*indirectly influence or modulate the effects of an agonist at a receptor
Benzodiazepines
o GABA is an inhibitory NT
o In its presence channels opens more readily and stays open longer

Question 31

antagonist

Answer 31

• Binding induces abnormal shape change those results in no signal transmission
• May bind at same location or other sites
  o Tagamet is an active site antagonist (turns off stomach acid)
   Binda to a histamine binding site (produces stomach acid)
   Distance b/w main binding domains larger than histamine

Question 32

allosteric antagonist

Answer 32

• Can bind near or partly inside of active site or distal location
• No longer able to bind to messenger

Question 33

partial agonist

Answer 33

• Agonist binds to receptor and produces non-ideal conformational change
  o Weak signal is sent
  o Enzyme wont be on long enough (bind weakly = weak reception)
   One binding gives agonism the other antagonism
• Buprenorphine (used to block the effects of opioid poisoning)

Question 34

inverse agonist

Answer 34

• Receptor gives weak signal to bind to messenger and then there’s an increase in strength of the signal
  antagonizes the effects of an agonist but, moreover, exerts the opposite effect by suppressing spontaneous receptor signaling
• Clozapine shows inverse agonist behaviour

Question 35

measuring drug behaviour

Answer 35

• Use biological assay (how fast cell grow)
• Qualitative (number)—how well it works
• In vitro
  o Using bio chemicals, cells or tissues
  o Always preferred easier and cheaper
• In vivo
  o Tests done in living animals

Question 36

general assay types

Answer 36

HPTS
routine SARS
* Kinetics or special studies
o Quantitative
* Cell based
o Antibiotics, antivirals, anti-cancer, metabolism studies
o Result of several properties
* Tissue based
o Permeability and complex