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DESIGNING
NEW MEDICINAL DRUGS
START
INGRID EDWARD
DESIGNING NEW MOLECULESTO FIGHT DISEASES
------STRUCTURAL FEATURES THE NEW DRUG
• stop particular bacteria or viruses working
• structural features may be associated with the active
site on a particular enzyme (essential for the pathogen)
structural features
predict
shape of the molecule
block into
the active site effectively
1. Hydrogen bonding
Intermolecular bonds
2. Ionic attraction
3. Dipole-dipole forces
4. Instantaneous dipole-induced dipole force
potential drug molecule and target molecule
judger
receptor site
Why do I use this picture?
synthesis a new medicine:
trails and errors
more testing
Computer is a powerful tool to help us.
A kind of polymer
Design medicines,
Design other compounds.
•Pesticides
•Polymers
pesticides
Introduction:
This type of research was used in the fight against AIDS in the late 1980s and 1990s.
X-ray crystallography was used by the scientists, they found and worked out the shape
of HIV protease. HIV protease is vital when the virus become infectious.
Catalytic cycle of an enzyme
Researches and scientists
found out that if block the
active site, this might be one
step on the route to finding a
cure for AIDS.
They also utilize the
computer to model the
distinct shape of enzyme
substrate. Because the
enzyme molecules are
extremely small, they use
the computer to maximize
the image under the
microscope.
FIRST TRIAL
THIRD
TRAIL
SECOND
TRIAL
PAY ATTENTION TO THE PEOPLE WHO ARE SURROUNDING YOU!
(HIV CARRIERS AND AIDS KILLERS CONFRONT NOT ONLY PAIN FROM
BODY, ALSO THE LONENESS AND HELPLESS!)
The first attempts fitted perfectly, but were not water soluble.
Problem:
The drug could not be delivered to its target.
The second attempts fitted superb, it become water soluble.
New characteristic:
•Water soluble.
•Interfere with the enzyme very well.
Researchers use less than 8 years, find out 3 different kinds of anti-viral
drugs for people with HIV/AIDS.
Methodology: trial-and-error methods
Third period:
You may wonder, the drugs are essential for cure the disease!
Something happened severely and potentially!
So scientists now have to model the new drug-resistant strains of the
infection and re developing new drugs to inhibit the mutant versions of
HIV protease.
These inhibitors are one part of a cocktail of drugs that can be treat the
disease now.
At least one chiral centre
Definition of chiral centre:
A molecule contains a carbon atom bonded
to four different atoms or groups of atoms.
Some of the pharmaceutical activity may occur disaster:
Naproxen is a drug used to treat the pain caused by arthritis
One enantiomer will ease the pain but the other
can cause liver damage.
The chemists change the chiral centre of
right figure, use the other components
changing the basic functional group.
One kind of medicine utilize it for conquer
the TB (tuberculosis) is effective whereas
the other kind of enantiomer can cause
blindness.
汉语意思是“对映体”，指的是互
为实物与镜像而不可重叠的一
对异构体。如左旋乳酸与右旋
乳酸是一对对映体。 对映体具
有相同的物理性质(如熔点，沸
点，溶解度，折射率，酸性，
密度等)，热力学性质(如自由能
，焓、熵等)和化学性质。除非
在手性环境(如手性试剂，手性
溶剂)中才表现出差异。对映体
对偏振光的作用不同，它们的
比旋光度数值相同，但方向相
反。等量的左旋体与右旋体的
混合物构成外消旋体。从对映
体中分离出单纯一个光学异构
体的方法称拆解。最普通的拆
解方法是将消旋体与光学活性
相反的离子(称拆解剂)作用生成
非对映体。
These two paragraphs told
us two distinct parts of the
nature of enationmer.
In chemistry, an enantiomer is one of two
stereoisomerism that are mirror images of
each other that are non-superposable (not
identical), much as one's left and right hands
are the same except for opposite orientation.
Organic compounds that contain an
asymmetric (chiral) Carbon usually have two
non-superimposable structures. These two
structures are mirror images of each other and
are, thus, commonly called enantiomorphs
(enantio = opposite ; morph = form) Hence,
optical isomerism (which occurs due to these
same mirror-image properties) is now
commonly referred to as enantiomerism
Enantiopure compounds refer to samples
having, within the limits of detection, molecules
of only one chirality.
Benefits of using pure
enatiomers:
1. Reduces the patient’s dosage by half
as the pure enationmer is more
potent, cutting costs and minimizing
the risk of side-effects.
2. Protect drugs companies from
possible litigation as people will sue
for damage when serious side-effects
do occur.
Three ways to prepare pure
enatiomers:
•Optical resolution
•Use optically active starting
materials
•Using a chiral catalyst.
Separate the two enantiomers-----optical resolution.
Optical resolution describes the ability of an imaging system to
resolve detail in the object that is being imaged.
An imaging system may have many individual components
including a lens and recording and display components. Each of
these contributes to the optical resolution of the system, as will the
environment in which the imaging is done.
Let us watch an animation
about optical resolution
and optical isomerism.
How to send the water-insoluble molecule to the target cell?
LASTED TECHNIQUES:
Using the non-cage of gold, why? Gold particles can be selectively absorbed by
tumors (thin, leaky blood vessels with holes and gold particles can pass through
it.)
Now doctors use the laser inject to the gold particles, gold particles absorb
the energy and get heat.
Heart cause the denature of protein in the tumor
which cannot destroy the healthy cells and tissues.
If we just put the gold particles into the
blood system, something will be
happened, our own immune system
would give the immune response to
eliminate the alien particles, so
researchers coated the gold particles
with the PEG (polyethylene glycol).
PEG will be distort in the hot
circumanstance and release the nanocage.
The first clinical use of a nano-particle was drug delivery by liposomes. Liposomes are
tiny membrane bubbles ,usually made of phospholipids. These molecules have a
hydrophilic head and hydrophobic tails.
Liposomes are useful delivering drugs because a water-soluble drug can be carried in
a aqueous solution inside the liposome and a drug which dissolves in fat can be
transported in the fatty layer of the wall made up of tails of the molecules. They are
also biodegradable and relatively non-toxic. As a drug-delivery system, liposomes can
achieve significant benefits for patients, for example, by reducing drug toxicity. This
works in cancer treatment in a similar way to the gold nano-cages injected into the
bloodstream. The liposomes are similar in size and can get through the loosely
packed walls of a tumor’s blood vessels, but not through the walls of healthy blood
vessels. Again, like gold nano-cages, they can have surface coatings added to avoid
attack by the immune system.
Liposomes can also fuse with cell membranes which have a similar structure and
deliver their contents inside the cell. They are used not only to carry drugs but also to
carry DNA for gene therapy. They are used to deliver wrinkle creams deeper into the
skin.
Fat-soluble drug is transported dissolved in
the fatty layer.
Water-soluble drug or DNA in aqueous
solution to be transported inside the sphere.
Hydrophilic------head
Hydrophobic------tail
•SOME DEFINITION CAME FROM WIKISPACES.
•SOME PICTURE FROM THE INTERENET.
ISBN 978-0-51-12661-8
•SOME PARTICLES AND SHORT-CUT GRAGH FROM TEXTBOOK.