Chapter 8 Med Chem

Receptor function. most receptors are located__. receptors are activated by ___ (__ or ___).

cell membrane, chemical messengers, neurotransmitters, hormones.

receptors contain a binding site ___ or ___in the receptor surface that is recognized by the _____.

hollow, cleft, chemical messenger

binding of messenger involved _____.

intermoelcular bonds

binding results in an ____ of the receptor protein

induced fit

change in receptor shape results in a __ effect.

domino

Domino effect is known as __ leading to a _ being received inside the cell.

signal transduction, chemical signal

chemical messenger does not enter the cell. It departs the receptor __ and is not permanently bond.

unchanged

A hydrophobic hollow or cleft on the receptor surface __ to the active site or an enzyme.

equivalent

Binding site, ___ and __ amino acids which bind the messenger

accepts, binds

the binging site contains __ which bind the messnger

amino acids

the binding site has __ or _ that takes place.

reaction, catalysis

messenger binding. binding site is nearly the _____ for the messenger.

correct shape

binding alters the shape pof the receptor __.

induced fit

what are the bonding forces of messenger binding

ionic, h bonding, van DER waals.

what are the substrate binding bonding forces.

indicued fit

binding interactions must be strong enough to hold the messsenger sufficiently long for ___ to take place

signal transduction

inteeracions must be __ enought to allow the messenger to __

weak, depart

implies a fine __ of binding interaction

balanceme

ssengers tend to ___ and ____ quickly

bind depart

__ are drugs designed to mimic thenatrual messenger

agonists

agonists soukd bind and leave quickly number of binding interactions is _

imploratnat

__ are drugs designed to block natural messenger

antagonists

antagonsts tend to have ___ and or more ___ resulting in a different induced fit that the receptor is __ acticated

stronger, binding interaction, not

agonists bind ___ to the binding site and produce the same ___ as the natural messenger the receptor is ___.

resversibly, induced fit, activated

agaonists are often __ in structure to the natural messenger

similar

the agonist must have the __ binding group

correctbind

binding groups must be ___ to interact with complementary binding regions (agonists)

correct th

The drug must have the ___ shape to fit the binding site

correct

design of an agonist

identify important ______ in _____. agonists are designed to have ____ capable of same interactions. usually require __ number of interactions.

binding interactions, natural messenger, functional groups, same number

design of agonistsy

must be positioned usch that they can interact with __ regions at the same time. example have has three binding groups but only two can bind simultaneously. this will have poor activty.

binding groups, complementary binding

design of agonsists. one __ of a chial drug normally binds more effectively than the other. different __ likely to have different biological properties.

enatiomer, enatiomers

agonists must have correct and __ to fit binding site

size and shape

agonists. groups preventing access are called ____ or ____.

steric Shields, steric blocks

Allosteric modulators

Agents which enhance receptor activity by binding to an ___ binding site rather than the ______.

allosteric, messenger binding site

example of a allosteric modulator

benzodiazepines in GABA receptor

Allosteric modulator do a g protein coupled receptor called the ___ receptor. used to treat __ problems

calcium sensing, thyroid

Antagonists bind __ to the binding site.

reversiblyi

___ bonds involved din binding reversible antagoinsts

intermoleculardi

(rev)differen induced fit means receptor is __ activated

nott

(rev)he anstonists ___ any reaction

does not undergole

l(rev) evel of antagonism depends on the strength of antagonists and _

binding, concentration

(rev)messenger is ___ from the binding site in reversible antagonists

blocked

(rev) increasing the messenger concentation __ antagonism

reverses

(rever)Design of antagonists antagonists bind to the ___ but fail to produce the ____ - receptor is not activated. the normal messenger is __ from binding.

binding site, correct induced fit, blocked

(rever)in antagonists the receptor bdining site changes shape?

no

antagonists can form binding interactions with bending regions in the binding site ____. (reversible

not used by the natural messsenger

(reversible)design of antagonsts: different induced fit resulting from extra binding interaction produces an induced fit hat

fails to activate the recepto

knowing the shape and characterists of a receptor binding site allows us to design drugs that act as agonists or antagonists. determining the receptor binding site layout is very difficult. 4 ways

synthesis large number of compounds and see which beinds betterment x ray crystal, genetic energieering of proteins, molecular modeling

irreversible antagonnists

antagonists binds __to the bdining site. different induced fit means that the receptor is_ activated . ___ is formed between the drug and the receptor. mesenger is from the binding site. increasing concentration __ antagonism. often used to _ receptor.

irreversibley, not, covalent bond, blocked, does not reverse, label

allosteric antagonist antagonist binds to an allosteric binding site. __ forms between _ and _. induced fit _ the shape of the receptor. binding site is _ and is _ recognized by the messenger. increasing messenger concentration _ antagonism.

intermolecular bonds, antagonist, binding site, alters, distorted, not , does not reverse

antagonists by the umbrella effect. antagonsists bind _ to a neighboring binding site. _ overlaps the _. messenger is _ from binding site.

reverisbly, antagonists, messenger binding site. blocked

Partial agonsists agents which act as _ but produce _ effect

agonists, weaker

partial agonsists. agent binds but does not produce the ideal _ for max effect. agent binds to binding site in two different modes, one where the agent acts as an _ and one where it acts as an _.

induced fit, agonist, antagonist.

inverse agonists

properties shared with antagonists

bind to receptor bindind site with a _ from the _.

receptor is __ activated

Normal messsenger is __ from binding to the bdining site.

different induced fit, normal messenger, not, blocked

inverse agonists

properties shared with antagonists

• bloc any inherent activity related to he receptor (_,_,_)

• inherent activity - level of activity presence in the _ of a chemical messenger

  • receprot are in an _ between constitutional active and inactive form

gaba, serotonin, dihydrophyridine receptor, absense, equilibrium

receptors become _ on long term exposure to agonists

desensitized

desensitation

prolonged binding of _ leads to phosphorylation of receptors _ or _. _ receptors changes shape and is _. _ occurs once agonist departs.

agonist, hydrozyl, phenolic group, phosphorylated receptor, inactivated, dephosphorylation

Sensitzation

cell synthesisises more _ to compensate for blocked receptors. cells become more sensitive to _. can result in _ and _. increased doeses of are required to achieve same effect (_). cells are supersensitive to normal neurotransmitter. causes withdrawal symptoms when agonists _. leads to dependence

receptors, natural messenger, tolerance, dependence, tolerance,with drawl.

_ is a steroid hormone that affects the _ and _ of a number of tissues.

estradiol, growth, development

The binding cite of estradiol

estrogen intracellular receptor

estradiol. binding induces a _, _, and a _ folding across the binding site as a lid.

conformational change, dimizeration, helical section

_ regions are exposed to binding with a _ protein. The nuclear transcription factor then binds to a specific portion of DNA and switches on transition of a gene resulting in synthesis of a protein.

af2 (activating), coactivator

the study of how moleculars interact with targets (enzymes, receptors) to produce a pharmacological effect

pharmacodynamics in vitro

the study of how the body interacts with the drug (ADME)

pharmacokinetics in vivo

_ antagonist for estrogen receptor (anti cancer agent)

tamoxifen

binding interactions for estradiol.

_ and _ of estradiol are important binding groups.

binding site is specious and _.

_ of estradiol is positioned in narrow slot.

orientated rest of molecule.

acts as an _.

phenol, alochol, hydrophobic, phenol group, agonist

binding interactions for raloxifene.

raloxifen is an _ used to treat _.

phenol groups mimic _ and _ of estradiol.

interaction with _ is important for antagonst activity.

side chin prevents receprot helix _ folding over as lid.

AF-2 binding regions is _ revelaed.

_ cannot bind.

antagonist, breast cancer, phenol, alochol, asp 351, H12, not, co activator