It tells about a brief introduction about the use of synthetic peptides as drug uses in daily life.

1. Synthetic peptide as drugs
Presented by
UJJAIN CHAURASIA
ROLL NO.-215CH001
Under the supervision of
Dr. RIMA THAKUR
DEPARTMENT OF CHEMISTRY
NATIONAL INSTITUTE OF TECHNOLOGY, PATNA
ASHOK RAJPATH PATNA , BIHAR (800005)
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2. Introduction
The term protein is used for molecule composed of over 50
amino acids, and peptide for molecules composed of less
than 50 amino acids.
There are 21 proteinogenic L-amino acids that in various
combinations and permutations,make up the peptides and
living things.

3. The first synthetic peptide was prepared by Emil Fischer a century
ago, but the medicinal use of synthetic peptides started after the
Second World War.
This was the time of oxytocin and vasopressin, cyclic
nonapeptides with one disulphide bridge, and of the
angiotensin's.
The synthesis of peptides was a long and difficult task, a
single peptide taking 1–2 years to produce by conventional
methods.
It was the genius of Bruce Merrifield, in 1963, who hastened and
automated this long process using the method the named Solid
Phase Peptide Synthesis (SPPS).
3
History

4. Virtually every life process involves
peptide in some way.
Biological role of peptides
Hormone realese
Blood sugar regulation
Bone metabolism
Neurological
processes

5. Peptides in drugs

6. Synthetic peptides
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This class of products, which embraces all peptides and
peptidomimetics made by chemical synthesis, are called
synthetic peptides. The types of synthetic peptides are
listed below:-
Marketed: >40 products
Pre-registration and
Phase II: >60 products
phase III: >20 products
 Gonadorelin Super-agonists
 Somatostatin Analogues
 ACE Inhibitors
 HIV Protease Inhibitors
 Vasopressin Analogues
 Calcitonin
 Immunostimulant Peptides

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Fig. 1. Molecular structures of the synthetic peptide ACE inhibitors.
Salient features of these synthetic peptides
 Extensive use in therapies of hypertension
 treatment of heart failure
 Highly specific drug
ACE Inhibitors
 The best known members of this family are Enalapril and
Lisinopril.
 Other well-known products in the class are Ramipril,
Trandolapril and Perindopril.

8. Gonadorelin Super-agonists
These peptides are used in endocrine cancers, especially in
prostate and breast cancers. The main drugs are listed below:-
 Leuprolide
 Buserelin
 Zoladex
 Triptorelin
 Nafarelin
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9. HIV Protease Inhibitors
There are ten HIV protease inhibitors approved by the FDA; those
inhibitors include:
 Saquinavir
 Indinavir
 Ritonavir
 Nelfinavir
 Amprenavir
 Fosamprenavir
 Lopinavir
 Atazanavir
 Tipranavir
 Darunavir
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10. General peptide synthesis
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Synthesis of Dipeptides Using Recycled CTC
Resin

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Approaches/Strategies for Effective
Development of Peptides as Drugs
A chemical modification of peptide and protein drugs improves
their enzymatic stability and/or membrane penetration of peptides
and proteins.
 PEGylation:- It describes the modification of biological
molecules by covalent conjugation with polyethylene glycol
(PEG), a non-toxic, non-immunogenic polymer. PEGylation
improves drug solubility, reduces proteolysis and decreases
immunogenicity.
 Substitution of one more L-amino acid with D-amino acids.
For e.g., Vasopressin and Desmopressin.
 Increasing the hydrophobicity of a peptide or protein by
surface modification using lipophilic moieties i.e. lipidisation
or multimerisation. For e.g., palmitoylation of insulin.

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Advantages and drawbacks of
peptides
 High activity, which
usually means that small
doses of peptide have to
be administered, and
also the total amount to
be produced is relatively
small.
 Peptides are usually
highly specific and have
therefore relatively low
systemic toxicity. They
do not accumulate in the
body as they have
relatively short half-
lives
 Their low bioavailability has the
consequence that they have to
be injected or special
formulations have to be
designed to accommodate them.
 The cost of their synthesis has
also been considered
disadvantageous. This could
change with larger scale
availability of all the products
needed, (protected amino acids,
coupling reagents, resins) and
also of the equipment and
products used in the
purification.

14. List of peptide drugs withdrawn
S.
No
Name of
drug
Drug
category
Therapeutic
indication
Reason for withdrawn
1. Drotrecogin
Alfa
Antisepsis For reduction of
mortality in patients
with severe sepsis.
It was not effective in
improving outcomes in
patients with sepsis
2. OspA
lipoprotein
Vaccines For prophylactic
treatment of Lyme
disease
Due to poor market
performance, and
economic concerns
3. Fusafungine Antibiotic Treatment of nasal,
throat and other
respiratory infections
Risk of potentially fatal
allergic reactions
4. Aprotinin serine
proteinase
inhibitors
/trypsin
inhibitors
For prophylactic use
to reduce
perioperative blood
loss
Increased risks of
complications or death
during surgeries, as
compared with alternate
medications
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15. New formulations for peptide
Solving the problem of injection of peptides, and proteins, has
been the theme of much research and development for many
years. New formulations can be of various kinds:
 Biodegradable polymers
 Non-degradable implants
 Liposomes
 Transdermal injection
 Inhalation
 Polymer coated pellets for oral administration
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16. Conclusions
 The triggering of specific receptors, or modulation of
enzymatic activity, can be done in a potent and specific way
using these synthetic peptides.
 synthetic peptides still suffer from a deficit in image ‘because
they have to be injected.
 As if erythropoietin or insulin had to be taken orally to be a
blockbuster! Times will probably change because solid phase
synthesis will be used more and more, allowing easier
production of relatively long peptides or short proteins.
 In the case of emergency treatments the speed of action and
the low side-effects of a peptide injection is unbeatable.
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17. References
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1. Duro-Castano, A.; Conejos-Sánchez, I. and Vicent, M.J., Peptide-
based polymer therapeutics. Polymers 2014, 6, pp.515-551.
2. Veronese, F.M.; Mero A. The impact of PEGylation on biological
therapies. BioDrugs 2008 ,22,315–329.
3. Ram IM.; Ajit SN.; Laura T.; Duane DM. Emerging trends in oral
delivery of peptide and protein drugs. Crit Rev Ther Drug Carrier
Syst 2003 ,20,153–214.
4. Hashimoto M.; Takada K.; Kiso Y.; Muranishi S.Synthesis of
palmitoyl derivatives of insulin and their biological activities. Pharm
Res 1989, 6,171–176.
5. Jani, P.; Manseta, P; Patel V.S. Pharmaceutical approaches related to
systemic delivery of protein and peptide drugs: an overview. Int J
Pharm Sci Rev Res 2017 12,42–52

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