Peptidomimetics are compounds that mimic natural peptides and proteins in 3D space. They are created by modifying the side chain or backbone of peptides. Peptidomimetics are designed to be highly selective, bioavailable, and metabolically stable.

1. PEPTIDOMIMETICS
SAGAR SHARMA

2. INTRODUCTION
PEPTIDOMIMETICS
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• To mimic a peptide.
• A peptidomimetics is a small protein-like chain
designed.
• They are typically arise from modification of an
existing peptide, or by designing similar
systems that mimic peptides, such as proteins
and β-peptides.
• For e.g. anticancer peptidomimetics can bind to
target proteins in order to induced cancer cells
into a form of programmed cell death called
apoptosis by mimicking key interactions that

3. CLASSIFICATION
1. TYPE -I PEPTIDOMIMETICS or PSEUDOMIMETICS
• These are synthesized by structure based drug design.
• These peptidomimetics are closely similar to peptide backbone while
ret functional groups that makes important contacts with binding sites
of the receptors.
2. TYPE-II PEPTIDOMIMETICS or FUNCTIONAL MIMETICS
• These peptidomimetics are synthesized by molecular modeling and
high through put screening (HTS) etc.
• These are small non-peptide molecule that binds to a peptide receptor.
• Morphine was the first well-characterized example of this type of
peptidomimetic.
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PEPTIDOMIMETICS

4. CLASSIFICATION
3. TYPE-III PEPTIDOMIMETICS or TOPOGRAPHICAL MIMETICS:
• These are synthesized by structure based drug design which
represents that they possess novel templates, which appear unrelated
to the original peptides but contain the essential groups, positioned on
a novel non-peptide scaffold to serve as topographical mimetics.
4. TYPE-IV PEPTIDOMIMETICS or NON-PEPTIDE MIMETICS:
• These are synthesized by Group Replacement Assisted Binding
(GRAB) technique of drug design.
• These structures might share structural functional features of type I
peptidomimetics, but they bind to an enzyme form not accessible with
type I peptidomimetics for example piperidine inhibitors.
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PEPTIDOMIMETICS

5. THERAPEUTIC VALUES OF
PEPTIDOMIMETICS
1. Anti-microbial activity
Srinivas et al. developed some novel peptidomimetic antibiotics
based on the antimicrobial peptide protegrin I to combat the growing
health threat posed by resistant pathogenic microorganisms. Several
rounds of optimization gave a lead compound that was active in the
nanomolar range against Gram-negative Pseudomonas species.
2. Anti-malarial activity
Ettari et al. synthesized some novel peptidomimetics bearing a
protected aspartyl aldehyde warhead leading to the thioacetal and the
acylal derivatives. Both Compounds proved to possess an increased
antiplasmodial activity with respect to the parent molecule.
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PEPTIDOMIMETICS

6. THERAPEUTIC VALUES OF
PEPTIDOMIMETICS
3. Anti-viral activity
In the search for new and effective prodrugs against the herpes simplex virus, a
series of acyclovir analogues with a thiazole ring containing amino acids (glycine,
alanine, valine, leucine) was investigated by Georgi et al.
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PEPTIDOMIMETICS

7. THERAPEUTIC VALUES OF
PEPTIDOMIMETICS
4. Anti-cancer activity
Yung-Feng et al. synthesized some novel
unnatural amino acid-substituted (Hydroxyethyl)
urea peptidomimetics which inhibited secretase,
the neuronal differentiation of neuroblastoma cells
and also interfered with tumorigenesis and the
malignancy of neuroblastomas. Which shows that
these peptidomimetics can be used as lead
compounds for further development of novel
anticancer drugs.
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PEPTIDOMIMETICS

8. BY MANIPULATION OF THE
AMINO ACID
• The physical and chemical properties of peptides and proteins are
determined by the nature of the constituents amino acids side chains and by
the polyamide peptide backbone itself.
• There are various primary amino acids are present. Amino acid are divided
into hydrophobic and hydrophilic residues.
• Small peptides typically show high conformational flexibility due to the
multiple conformations that are energetically possible for each residues.
• It is a nucleophilic amino acid. It is a hydrophobic amino
acid.
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PEPTIDOMIMETICS

9. MODIFICATION OF PEPTIDE
BACKBONE
• The backbone of isoelectric and isoelectronic substitution.
• Various peptidomimetics or peptide bond surrogates, in which peptide
bonds have been replaced with other chemical groups, are designed
and synthesized with the aim to obtain peptide analogs with improved
pharmacological properties.
• This is mainly because such approaches create an amide bond
surrogate with defined 3 dimensional structures and with significant
differences in polarity hydrogen bonding capability and acid-base
character.
• Also important, the structural and stereochemical integrities of the
adjacent pair of alpha carbon atoms in these
pseudopeptides are unchanged.
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PEPTIDOMIMETICS

10. INCORPORATING CONFORMATIONAL
CONSTRAINTS LOCALLY OR
GLOBALLY
Local Restrictions
• The simplest constraints that can be placed
on a given residue involve the substitution of
methyl group for an hydrogen adjacent to
a rotatable bond.
• Example- Replacing the alpha hydrogen on
• alanine with methyl group gives
• α-aminoisobutyric acid(AIB).
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PEPTIDOMIMETICS

11. INCORPORATING CONFORMATIONAL
CONSTRAINTS LOCALLY OR
GLOBALLY
Global Restrictions
(A) head-to-tail
(B) backbone-to-side chain
(C) Side chain-to-side chain
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PRESENTATION
TITLE

12. INCORPORATING CONFORMATIONAL
CONSTRAINTS LOCALLY OR
GLOBALLY
• This typically increases the in vivo stability of the cyclic peptides
compared to their linear analogs.
• Cyclization can be obtained by connecting the N-with the C-terminus
(head to tail) portion of the peptide sequence ,or the couple of the
either the N-or the C- terminus with one of the side chains (backbone-
to-side chain), or the couple of side chains not involved in specific
interactions with other (side chain-to-sidechain)
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PEPTIDOMIMETICS

13. CHEMISTRY OF
PROSTAGLANDINS
• Prostaglandins are a group of naturally occurring substances
synthesized primarily in the prostrate. They are widely distributed in
mammalian tissues, e.g., lung, kidney and thyroid. Prostanoic acid.
• Prostaglandins have a common structure based on
prostanoic acid which contains 20 carbon atoms.
• They are separated into four groups A, B, E and F
depending on the variations in the double bonds
and in the hydroxyl and ketone groups.
• The carbon chains are bonded at the middle of the chain by a 5-
memberedring.
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PEPTIDOMIMETICS

14. CHEMISTRY OF
PROSTAGLANDINS
• A, B and E have an oxo-grouping at position 9, whereas F has a hydroxyl
group in this position.
• A has a double bond between positions 10 and 11, whereas B has a double
bond between positions 8 and 12. E and F do not have a double bond in the
ring but possess a hydroxyl group at position 11.
• All active prostaglandins have at least one double bond between positions 13
and 14. Some have two double bonds, the second being between positions 5
and 6 and some prostaglandins have three double bonds, the additional bond
being between positions 17 and 18.
• The common single double bond has the trans-configuration, whereas the
other double bonds have the cis-configuration.
• All prostaglandins have a hydroxyl group at position 15 and some have
another hydroxyl group at position 19.
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PEPTIDOMIMETICS

15. CHEMISTRY OF
LEUKOTRIENES
• Leukotrienes are a family of eicosanoid inflammatory mediators
produced in leukocytes by the oxidation of arachidonic acid(AA) and
the essential fatty acid eicosapentaenoic acid (EPA) by the
enzymearachidonate5-lipoxygenase.
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PEPTIDOMIMETICS

16. CHEMISTRY OF
LEUKOTRIENES
• Simple dehydration with a proton removed from C-10 gives an epoxide
ring at C-5 and C-6, and three conjugated double bonds between C-7
and C-12. This is leukotriene A4 (LTA4) .
• The triene designation refers to the signature ultraviolet spectrum due
to three conjugated double bonds.
• The subscript denotes the total number of double bonds - four when
derived from arachidonate.
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PEPTIDOMIMETICS

17. CHEMISTRY OF
THROMBOXANES
• Thromboxane is a member of the family of lipids known as
eicosanoids. The two major thromboxanes are thromboxanes A2 and
OH thromboxane B2. The distinguishing feature of thromboxanes is a
6-membered ether containing ring.
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PEPTIDOMIMETICS

18. CHEMISTRY OF
THROMBOXANES
• The two major thromboxanes are thromboxane A2 and thromboxane
B2. The distinguishing feature of thromboxanes is a 6-membered ether-
containing ring.
Thromboxane A2 Thromboxane B2
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PEPTIDOMIMETICS

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