This document discusses peptidomimetics, which are molecules that mimic peptides but do not contain peptide bonds. Peptidomimetics have increased bioavailability and duration of action compared to peptides. There are four types of peptidomimetics: Type I mimic peptide backbones, Type II are small molecules that bind peptide receptors, Type III have novel scaffolds that position essential groups, and Type IV are non-peptide molecules. Peptidomimetics have various therapeutic applications including antimicrobial, anticancer, antiviral, and antioxidant activities. They can be designed by replacing parts of peptides with non-peptide moieties or by hypothesizing the bioactive peptide form. Manipulating amino acids or their side chains allows creating

1. THERAPEUTIC VALUES OF PEPTIDOMIMETICS
AND
DESIGN OF PEPTIDOMIMETICS BY MANIPULATION OF
AMINOACID
Presenting by:
Mr. Purushotham K.N
Assi.Prof.Dept.Of.Ph.Chemisty
SACCP.
2021-2022

2. CONTENTS
1. Intoduction
2. Therapeutic values of peptidomimetics
3. Design of peptidomimetics by manipulation of the amino acid

3. INTRODUCTION
Peptides : A peptide is a compound that consists of at least two amino
acids linked by an amide group.
Eg : Alanine-Valine-Glycine(Ala-Val-Gly) . It is a tripeptide.

4. PEPTIDOMIMITICS
• Molecules that mimic the action of peptides, have no peptide bonds
and have a molecular weight of less than 700 daltons.
• It increases the bioavailability and duration of action.
• Majority of peptidomimetics are have been discovered by random
screening technique.
• This method is costly, labor intensive and unpredictable.

5. TYPES OF PEPTIDOMIMETICS
1. Type-I peptidomimetics or pseudopeptides: These are synthesized by
structure based drug design. These peptidomimetics are closely
similar to peptide backbone while retaining 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
throughput screening (HTS) etc. These are small non-peptide
molecule that binds to a peptide receptor.
Eg: G-protein coupled receptor antagonist.

6. 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

7. THERAPEUTIC VALUES OF PEPTIDOMIMETICS
1. Antimicrobial activity
2. Anticancer activity
3. Antiviral activity
4. Immunodetection activity
5. Selectivity for DNA receptors
6. Antimalarial activity
7. Antioxidant activity

8. Antimicrobial activity:
Srinivas et al. developed some novel peptidomimetic antibiotics based
on the antimicrobial peptide protegrin І to combat the growing health
treat 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.
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

10. Antiviral 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. The chemical stability of some of the compounds
containing different residues was studied at pH 1 and pH 7.4 at a
temperature of 37°C.

12. Selectivity for DNA receptors:
A peptidomimetic template, consisting of a hydrophobic scaffold, a
dansyl fluorophore, and an Arg-His recognition strand, was tested by
Jeffrey et al. as a simple mimic of zinc finger of the Zif26 protein

13. Anti-malarial activity:
Ettari et al. synthesized some novel peptidomimetics bearing a protected
aspartyl aldehyde warhead leading to the thioacylal derivatives. Both
compounds proved to possess an increased antiplasmodial activity with
respect to the parent molecule .
Anti-oxidant activity:
A series of related biocompatible imidazole-containing peptidomimetics were
synthesized in order to confer resistance to enzymatic hydrolysis and ex vivo
improvement of protective antioxidative properties related to carnosine.

14. DESIGN OF PEPTIDOMIMETICS BY MANIPULATION OF
THE AMINO ACID
There are two different approaches to design peptidomimetics:
• Medicinal chemistry approach: where parts of the peptide are
successively replaced by non-peptide moieties until getting a non-
peptide molecule
• Biophysical approach: where a hypothesis of the bioactive form of
the peptide is sketched

16. • Design of peptidomimetic chemistry is connected to the development
of compounds capable of replacing one or more aminoacids in a
peptide sequence without altering the biological activity.
• Access to novel amino acids as peptide bioisosters has been persued
by
 Either modifying the atoms involved in backbone formation of a
peptide or in manipulating the side chain moiety,
 Peptidomimetic chemistry has been oriented to the development of
higher isosters, taking into account di ,tri or tetrapeptides to be
replaced by more complex molecular architectures.

18. REFERENCE:
1. https://www.slideshare.net/MahendraMahi28/peptidomimitics
2. https://pubs.rsc.org/en/content/articlelanding/2014/cs/c3cs60384a
3. https://badge.dimensions.ai/details/id/pub.1104166931
4. Therapeutic importance of peptidomimetics in medicinal chemistry
Rajeev Kharb 1 *, Meenakshi Rana1 , Prabodh Chander Sharma2 ,
Mohammad Shahar Yar3

19. THANK YOU