Peptidomimetics are small protein-like chains designed to mimic peptides and can be derived from existing peptides or designed structures, aiming to improve stability and biological activity. The document discusses their classification, advantages such as enhanced activity and better transport properties, and disadvantages like limited stability and potential side effects. Additionally, it covers methods of modification and highlights recent advancements, including their application in peptide vaccines and antimicrobial peptides.

2. Contents
• Introduction
• Classification
• Advantages and Disadvantages
• Method of preparation
• Peptidomimetics Drug Design Principle
• Chemistry and stereochemistry
• Synthesis
• Therapeutic value of peptidomimetics

3. Introduction
• A small protein – like chain designed to mimic a peptide , have
no peptide bonds and MW<700D
• Arise either from –
 Modification of an existing peptide,
 or by designing similar systems that mimics peptides, such as
peptoids and β-peptides.
• Altered chemical structure is designed to adjust the molecular
properties as, stability or biological activity.

4. Defination
 Peptidomimetics are
chemical structures derived
from bioactive peptides
which imitate natural
molecules.
 A peptidomimetics is a
small protein – like chain
designed to mimic a
peptide. They typically arise
either from modification of
an existing peptide, or by
designing similar system
that mimic peptides, such
as peptoids and β-peptides .

5. Classification
Chart No: 1
Class A
• Modified peptides: peptides mainly formed by α-amino acids
with minor side chain or backbone alterations.
Class B
• Modified peptides/ foldamers: peptides with various
backbone and side chain alteration also including foldamers.
Class C
• Structural mimetics: small molecules-like scaffolds that
project substituents in analogy to peptide side chains.
Class D
• Mechanistic mimetics: molecules that mimics the mode of
action of a peptides without direct link to its side chains.

6. Advantages and Disadvantages
 Advantages of Peptidomimetics as Drugs
1. Conformationally restrained structures
can minimize binding to non-target
receptors and enhance the activity at the
desired receptor.
2. Addition of hydrophobic residues and/or
replacement of amide bonds results in
better transport properties through
cellular membranes.
3. Isosteres, retro-inverso peptides, cyclic
peptides and non-peptidomimetics all
reduce the rate of degradation by
peptidases and other enzymes.
 Disadvantages of Peptides as Drugs
1. Limited stability towards proteolysis
by peptidases in the gastroeintesinal tract
and in serum (t1/2 on the order of
minutes)
2. Poor transport properties from the
intestine to the blood and across the
blood-brain barrie due to high MW and
lack of specific transport systems
3. Rapid excretion through the liver and/or
kidneys
4. Inherent flexibility enables interaction
with multiple receptors besides the target,
and could result in undesired side-effects

7. Methods of modification

8. Retro-Inverso Peptidomimetics

9. Morphine: a Non-peptidomimetics
For Enkephaline

10. Somatostatine:Early Investigations

11. Peptidomimetic HIV-1 Protease
Inhibitors

12. Peptidomimetics Drug Design Principle

13. Chemistry and Stereochemistry

14. Synthesis

15. Therapeutic Value of Peptidomimetics
INNs Brand names Length Sequences Companies Indications Half-life
Daptomycin Cubicin 13 aa N-Decanoyl-Trp-Asp-Asp-
threonylglycyl-ornithyl-Asp-D-
alanyl- aspartylglycyl-D-seryl-
threo-3-methyl- glutamyl-3-
anthraniloyl-alanine[egr]1-
lactone
Cubist
Pharmaceutical
s
Antibiotic used to treat
systemic and life-
threatening infections
caused by Gram-
positive organisms
8–9
hours
Afamelanotid
e
Scenesse 13 aa Ac-Ser-Tyr-Ser-Nle-Glu-His-D-
Phe-Arg- Trp-Gly-Lys-Pro-Val-
NH2
Clinuvel
Pharmaceutical
s
Erythropoietic
porphyries
100 min
Eptifibatide Integrilin 7 aa c[Mpa-homoArg-Gly-Asp-Trp-
Pro-Cys]- NH2
Millennium
Pharms, GSK,
Schering-Plough
Acute coronary
syndrome, unstable
angina undergoing PCI
2.5 hours
Cyclosporine Neoral, Gengraf,
Sandimmune,
Arpimune Me,
Graftin,
Imusporin,
Panimun Bioral
11 aa (3S,6S,9S,12R,15S,18S,21S,24S,
30S,33S)- 30-Ethyl-33-
[(1R,2R,4E)-1-hydroxy-2-
methyl-4-hexen-1-yl]-
6,9,18,24- tetraisobutyl-3,21-
diisopropyl-
1,4,7,10,12,15,19,25,28-
nonamethyl-
1,4,7,10,13,16,19,22,25,28,31-
undecaazacyclotritriacontane-
2,5,8,11,14,17,20,23,26,29,32-
undecone
RGP life
sciences,
Ranbaxy
laboratories,
Cipla limited,
Ecolity, Allergan,
Novartis
Transplant (kidney,
liver, and heart)
rejection, rheumatoid
psoriasis arthritis,
severe
5–18
hours

16. Recent Advances In Peptidomimetics
i. Peptides vaccines were developed for the
prevention and treatment of pathogenicity
diseases,cancer and autoimmune disorders but
because of low immunogenicity and reduced
bioavailability they have become unsuccessful
peptidomimetics were developed through
chemical alteration of epitope structure to
overcome this side effects.
ii. A new range of AMPs(antimicrobial peptides)
termed’’Peptidomimetics ‘’were developed to
mimic the bactericidal mechanism.