Learn about drugs derived from peptides

I. General introduction to peptides and their applications in drug research

1.What is a peptide?

-A peptide is a type of protein molecule that is smaller and simpler than a protein.
Proteins are molecules made up of a chain of amino acids linked together by peptide
bonds. Each protein has one or more polypeptide chains, and the function of the
protein depends on the structure and interaction between the polypeptide chains
within the protein.

-Peptides are often produced by cutting off some parts of the polypeptide chain from
a protein using various enzymes. This cutting process is called hydrolysis. Peptides
vary in length, from a few amino acids to several hundred amino acids. However,
most peptides are less than 50 amino acids in length.

-Peptides have many different functions in the body, including:

Participating in communication between cells: Peptides can act as a reflex of cell
stimulation, promote cell activity, or reduce cell activity.
Immunological mechanism: Peptides can activate or act as inhibitors in the body's
immune system.

-Food metabolism: Peptides are produced during food digestion and absorbed into
the blood to provide nutrients for the body.
-Other functions: Peptides can participate in other biological processes such as ion
exchange, nerve cell communication, regulation of development and cell
metabolism.
-In addition, peptides are widely used in medical and pharmaceutical fields, such as
in designing and producing new drugs, molecules that communicate between cells,
immune reactions, and in medical diagnostic methods.

2.Why are peptides used in drug research?

-Peptides are an important component in drug research because they have several
advantages over other compounds. Here are some reasons why peptides are used in
drug research:
+Cell interactions: Peptides have the ability to interact with cells and other molecules
in the body, allowing them to be used to regulate cell activity or prevent the
development of abnormal cells.
+High safety: Peptides have a high degree of safety and are less likely to cause
adverse reactions than other chemical compounds. This is because peptides are
naturally present in the body and are not toxic to cells.
+High selectivity: Peptides have a high degree of selectivity, meaning they can
interact with a specific type of cell or molecule. This allows researchers to identify
specific peptides that can interact with a particular target in the body.

+Easy to produce: Peptides can be produced in the laboratory using chemical

synthesis or biological techniques. Therefore, researchers can easily and efficiently
produce specific peptides for research purposes.

+Easy to customize: The properties of peptides can be customized by changing the

amino acids in the peptide chain. This allows researchers to create peptides with
different properties and activities to serve different research purposes.

-For these reasons, peptides are a useful tool in drug research, used to develop new
drugs, study the mechanisms of drug action in the body, and test the effectiveness of
diagnostic methods.

3.Applications of peptides in drug research and production

-Peptides have many applications in drug research and production, including:
Drug development: Peptides can be used to develop new drugs, especially in the
treatment of difficult diseases. Researchers can create specific peptides that can
interact with a particular target in the body and use them to design and develop new
drugs.
-Disease modeling: Peptides are also used to model diseases and study disease
mechanisms. Specific peptides can be used to model different diseases, helping
researchers understand disease mechanisms and search for effective treatments.

-Vaccine development: Peptides are also used to develop new vaccines. Researchers
can use specific peptides that mimic the structure of a virus or bacteria to stimulate
the immune system and create immunity to the pathogen.

-Diagnostic tools: Peptides can be used to develop diagnostic tools for diseases.
Specific peptides can be used to detect disease-specific markers in the body and
create sensitive and specific diagnostic tests.

-Overall, peptides are an important tool in drug research and have a wide range of
applications in the development of new drugs, disease modeling, vaccine
development, and diagnostic tools.

II:
A.Peptide Antibiotics: Consisting of 3 groups:
-Glycopeptide group: Vancomycin, Teicoplanin.
-Lipopeptide group: Daptomycin.
-Polypeptide group: Polymycin B, Colistin and Bacitracin.

1.Glycopeptide Group:
Used in cases of severe life-threatening Gram-positive infections, with or without
resistance to methicillin: Endocarditis, septicemia, osteomyelitis, meningitis, joint
infections, skin and soft tissue infections caused by Gram-positive bacteria resistant
to methicillin. Vancomycin is also used orally to treat Clostridium difficile infection
(CDI).
-Vancomycin:
Mainly used to treat drug-resistant Gram-positive infections.
Bactericidal effect is time-dependent, with synergy observed with aminoglycosides.
Mainly bactericidal, with bacteriostatic activity against enterococci.

-Teicoplanin:
Used to treat severe Gram-positive aerobes and anaerobes infections.
Teicoplanin has a chemical structure, mechanism of action, spectrum of activity, and
elimination route (elimination mainly through the kidneys) similar to vancomycin.

2.Lipopeptide Group:

The only approved drug in this group is Daptomycin.

It is inhibited by surfactant lung activity, so it cannot be used in pneumonia.
Bactericidal effect is concentration-dependent and rapid.
It has no cross-resistance with any other antibiotic group, and its post-antibiotic
effect is relatively prolonged in vitro.

3.Polypeptide Group:
This is a highly toxic group, so it is only used when no other antibiotics are more
effective. It can be neurotoxic: toxicity may occur in the first few days of treatment
and may be dose or rate-dependent, with toxicities including dizziness, muscle
weakness, confusion, headache, visual disturbance, loss of motor coordination, and
hypersensitivity reactions. Kidney toxicity is around 30%, and may or may not be
reversible.
Polymycin B and Colistin bind to the Phosphatidylethanolamine receptor only present
in Gram-negative bacteria, then bind to the LPS on the cell membrane to release
cations. They have a similar spectrum of activity. They are highly toxic, so they are
only used for intravenous treatment of MDR and PDR strains, or for topical use.
(Illustration below shows the mechanism).
-Bacitracin is a mixture of cyclic peptides produced by organisms belonging to the
licheniformis group of Bacillus subtilis var Tracy, first isolated in 1945. These
peptides disrupt Gram-positive bacteria by interfering with cell wall synthesis and
peptidoglycan formation. Due to its high nephrotoxicity, it is only used topically.

B. Peptide derivatives: Enfuvirtide, Ziconotide,...

1.Enfuvirtide:
Enfuvirtide is a HIV-1 gp41 fusion inhibitor used in patients who have undergone
treatment with other antiviral drugs. It is a biologically mimetic peptide consisting of
36 amino acids with a structure similar to the HIV proteins responsible for viral
fusion with cell membranes and subsequent internalization. The first agent in a new
class of antiviral drugs called HIV fusion inhibitors, enfuvirtide works by inhibiting the
fusion of HIV-1 with CD4 cells.

2.Ziconotide:
Ziconotide is a N-type calcium channel antagonist used to treat patients with severe
chronic pain who are intolerant to or do not fully respond to other treatments such as
intrathecal morphine and systemic analgesics. Also known as SNX-111, ziconotide is
a neurotoxic peptide derived from the cone snail Conus magus consisting of 25
amino acids with three disulfide bonds. Similar peptides, collectively called
conotoxins, exist and some have shown efficacy in binding specific subsets of
calcium channels. Ziconotide is used in part because it can be synthesized without
losing proper bond formation or structural factors. Ziconotide is used to control
severe, difficult-to-treat chronic pain by inhibiting N-type calcium channels involved in
nociceptive signaling. Ziconotide was approved by the FDA for marketing by TerSera
Therapys LLC on December 28, 2004, under the name Prialt. To date, ziconotide is
the only approved peptide calcium channel blocker for use by the FDA.

III. Mechanisms of action of peptide-derived drugs

1.How do peptide-derived drugs work?
-Peptide-derived drugs work by interacting with cell surface proteins or receptors,
inhibiting or activating them.
-Some examples of how a peptide-derived drug works:

+Octreotide binds to somatostatin receptors along with phospholipase C via G

proteins, leading to smooth muscle contraction in blood vessels. The downstream
effect stimulates phospholipase C, producing 1, 4,5-inositol triphosphate, and affects
L-type calcium channels leading to the inhibition of growth hormone, treating various
metabolic and growth hormone effects of acromegaly.
+Octreotide inhibits the release of growth hormone (GH), decreases blood flow to the
endocrine gland, and inhibits serotonin, gastrin, intestinal peptide, secretin, motilin,
and pancreatic polypeptide to help reduce the digestive and flushing symptoms of
carcinoid and/or VIPoma tumors.

2.The difference in the mechanism of action between peptide derivative drugs and
other drugs:
-Peptide derivative drugs often have different mechanisms of action compared to
other drugs. This can be explained by the natural properties of peptides, which are
low molecular weight molecules that can strongly interact with proteins and can be
specially designed to enhance their biological properties.

-An example of the difference in mechanism of action between peptide derivative

drugs and drugs:
The mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs work by inhibiting the action of the enzyme cyclooxygenase (COX), which
produces prostaglandins. During an infection, prostaglandins can act on the
hypothalamus, leading to increased body temperature and pain. Therefore, NSAIDs
inhibiting the action of COX will weaken the production of prostaglandins, leading to
a decrease in body temperature to a normal level.

-The mechanism of action of Enfuvirtide as an inhibitory compound prevents the

rearrangement of the HIV-1 gp41 structure and functions by specifically binding to
the virus's outer cell protein, thereby preventing the fusion of the virus cell membrane
and the target cell membrane, preventing the RNA virus from invading the target cell.

IV. Applications and effects of drugs derived from peptides.

Bacitracin:
It is a polypeptide antibiotic. It is a mixture of related cyclic peptides produced by the
bacterium Bacillus licheniformis. These peptides disrupt Gram-positive bacteria by
interfering with the cell wall and peptidoglycan synthesis. Bacitracin is a polypeptide
antibiotic that inhibits cell wall synthesis and is active against Gram-positive
bacteria.
Mechanism and action: Bacitracin interferes with the dephosphorylation of C
55-isoprenyl pyrophosphate and a related molecule called bactoprenol
pyrophosphate; both lipids function as membrane carrier molecules transporting the
building blocks of the bacterial cell wall peptidoglycan outside the inner membrane.
Some have claimed that bacitracin is an inhibitor of protein disulfide isomerase , but
this is disputed by in vitro studies
Polymyxin E and Polymyxin B
Colistin, also known as polymyxin E, is an antibiotic produced by certain strains of
the bacterium Paenibacillus polymyxa. Colistin is a mixture of the polypeptide rings
colistin A and B and belongs to the group of polypeptide antibiotics or polymyxins.
Colistin is effective against Gram-negative bacilli. Colistin is a polycationic peptide
and has hydrophilic and lipophilic groups. The cation region interacts with the
bacterial outer membrane by displacing magnesium and calcium ions in the
lipopolysaccharide. The hydrophobic/hydrophilic region interacts with the cell
membrane like a detergent, dissolving the membrane in aqueous media. The drug
has a bactericidal effect even in unipolar environments.

Polymyxin B is an antibiotic mainly used for meningitis, pneumonia, sepsis, and

urinary tract infections.[1] It is derived from the bacterium Bacillus polymyxa. The
drug is bactericidal against most Gram-negative bacilli except the genera Proteus
and Neisseria. Polymyxin B includes polymyxins B1, B1-I, B2, B3 and B6. Polymyxin
B1 and B2 are the main components. These related components are structurally
identical except for one fatty acid group that changes per part. Polymyxin binds to
cell membranes and changes its structure, making it more permeable. Water uptake
leads to cell death. Polymyxins are cationic, base peptides that act as detergents
(surfactants). Side effects include neurotoxicity and acute tubular necrosis.
Polymyxin is used in the topical first aid preparation Neosporin.
Reduces the permeability of the bacterial outer membrane by binding to a negatively
charged site in the lipopolysaccharide layer, which has electrostatic attraction for the
positively charged amino groups in the cyclic peptide fraction; As a result, the outer
membrane is unstable
The fatty acid fraction dissolves in the hydrophobic region of the cytoplasmic
membrane and disrupts the integrity of the membrane
Leakage of cellular molecules, inhibition of cellular respiration
Binds and inactivates endotoxins
Relative absence of selective toxicity: not membrane-specific of any kind, highly
toxic.

Palmitoyl Tripeptide-5
Palmitoyl Tripeptide-5 has the chemical formula C33H65N5O2.2(C2HF3O2), is made
up of amino acid chains and belongs to the group of signal peptides (Signal
Peptides). , especially high-end lines of famous brands. They are made up of chains
of amino acids, capable of penetrating the epidermis and deep into the dermis,
helping to stimulate collagen production and support the maintenance of healthy
tissues. In its natural state, Palmitoyl Tripeptide-5 is a clear, colorless, odorless and
water-soluble liquid. They have a very special mechanism of action, because they
can simulate the communication mechanism with cells, sending out natural signals
to help promptly remove harmful toxins from entering the body.
Uses of Palmitoyl Tripeptide-5
Penetrates deep into the skin, helping to stimulate collagen production and support
healthy tissue growth.
Can receive signals from skin cells, helping to prevent harmful substances from
entering in time. Provides very high skin care and skin care effects thanks to its good
penetration ability.
Helps speed up natural collagen synthesis, making skin youthful, firm and effective
anti-aging support.
Improves and builds the skin's foundation structure, enhances elasticity, improves
firmness and helps to make skin softer.

V. Standards for production of drugs derived from peptides and trends in discovery
of drugs with peptide derivatives.
An important aspect of rational peptide drug design is to improve the
physicochemical properties of natural peptides, which are often prone to
agglomeration and sometimes poorly soluble in water. Chemical design strategies to
avoid synthesis include the failure of hydrophobic fragments, which can be achieved
by substitution or N-methylation of specific amino acids. If solubility issues exist for
a given peptide drug candidate, the general area of focus is the charge distribution
and isoelectric point (pI) of the peptide, relative to the pH of the formulation. desired
end product.

The physicochemical properties of peptides can also be improved by the

introduction of stable α-helices, salt bridge formation, or other chemical
modifications, such as lactam bridges. Modifications introduced through rational
design to improve the physicochemical properties of a given peptide must be
consistent with the overall desired pharmacokinetic and pharmacokinetic properties
of the peptide therapy. The use of predictive IT software tools to facilitate such
streamlined peptide design is expected to increase in the future as these tools
become more and more user-friendly.
A peptide drug benchmark is a test that measures the quality, safety, efficacy, or
pharmacokinetics of a peptide drug or peptide drug delivery system. Peptide drugs
are compounds containing between 2 and 50 amino acids and have the potential to
treat various diseases, such as diabetes, cancer, infection or inflammation.
For example:
The purity and identity of the synthetic peptides, can be assessed by analytical
methods.
The stability and degradation of peptides, can be affected by factors such as
temperature, pH, light, oxidation or proteolysis. Stability testing can be performed by
measuring changes in peptide concentration, activity or structure over time.
Bioavailability and biodistribution of peptides, which may be affected by route of
administration, formulation, or the presence of barriers such as the skin or
blood-brain barrier
pharmacokinetics and pharmacokinetics of peptides, which may be affected by size,
charge, hydrophobicity or binding affinity of the peptide)

VI. Conclusion
Drugs derived from peptides are of great importance in the medical field, because
they have the ability to precisely interact with proteins and enzymes in the body,
thereby helping to treat various diseases effectively. more fruitful. These drugs are
made from peptide chains with special biological activity, then purified and put into
use in the treatment of diseases. These drugs have the ability to optimize treatment
effectiveness, while minimizing side effects and ensuring patient safety. Therefore,
drugs derived from peptides are considered as one of the most advanced and
effective solutions in the medical field.
Further developments in peptide drugs may include:
1. Therapeutic peptides: Peptide derivatives can be used as a medicine to treat
diseases such as cancer, arthritis and other diseases. Peptides can be engineered to
be more concentrated in the body and reduce unwanted side effects.
2. Peptide vaccines: Derivative peptides can be used to develop new vaccine
platforms. Selected peptides can stimulate the immune system to produce
antibodies against cancer cells or viruses.
3. Peptide drug conjugates: Peptide drug conjugates are multifunctional molecules
with a combination of one peptide and another drug. This drug has the potential to
be highly effective in treating diseases thanks to its high concentration and rapid
disease reduction.
4. Peptide stabilizers: Derivative peptides can be used to improve the stability of
other drugs by forming complexes with them, helping to keep hard-to-dissolve drugs
in soluble form.
5. Peptide biomarkers: Derivative peptides can be used for early disease detection
and disease progression monitoring. Finding peptide biomarkers could be a
significant step forward in disease diagnosis and patient assessment.