Download EMERGING TRENDS IN ANTIMICROBIAL PEPTIDES

EMERGING TRENDS IN
ANTIMICROBIAL PEPTIDES
DEVELOPMENT AND
APPLICATIONS
JITENDER MEHLA & Dr.R.A.SIDDIQUE
RESEARCH SCHOLARS,
ANIMAL BIOCHEMISTRY DIVISION
N.D.R.I., Karnal, (Haryana)
India
WHAT ARE AMPs?
PATHOGENS
HOST
INNATE IMMUNITY
DIFFERENT COMPONENTS
ANTIMICROBIAL PEPTIDES
Cont…
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Small peptides having app. 12-50 a. acids
Produced in most exposed tissues by induction or
constitutively
Synthesized at low metabolic cost
So far more than 800 AMPs have been described
Structure and Classification of
AMPs
Signal peptidase
PRE
29-30
residues
Elastase
PRO
98-114 residues
PEPTIDE
PEPTIDE
12- 50 residues
Classification of AMPs
CLASS
EXAMPLE
STRUCTURE ORIGIN
Anionic
peptides
Dermicidin
Asp & Glu
Human
Cationic
peptides
Cecropin
Helical
insects
LL37
Helical
Human
Pro & arg
rich
Pig
Prophenin
Pro & Phe
Pig
Indolicidin
Trp rich
cattle
Cationic
PR 39
peptides with
specific
amino acids
Cont….
Peptides that
forms
disulphide
bridges
Fragmented
peptides
Brevinins
1-disulphide
bridge
Amphibians
Tachyplesin
2-disulphide
bridges
Horse shoe
crab
Defensins
3-disulfide
bridges
Human
NK-lysin
3-disulfide
bridges
Pig
Drosomycin
More than 3disulfide
bridges
Fruitfly
Lactoferricin
14-42 a.acids Human
Transcriptional regulation of
AMPs
Taeil Kim et.al., 2005
Amino acid sequence of NKLysin
Sequence of NK-2
Antimicrobial
activity
KILRGVCKKIMRTFLRRISKDILTGK
K
1
5
1
0
1
5
20
25
NK-CS
Antimicrobial
activity
KLLRGVSKKIMRTFLRRISKDILTGKK
NKCS-[MS]
Antimicrobial
activity
KILRGVSKKISRTFLRRISKDILTGKK
NKCS-shortened analogues
KLLRGVSKKIMRTFLRRISKKDILTGKK
NKCS- [20K]
Antimicrobial
activity
KILRGVSKKIMRTFLRRISK
K
NKCS-[RKK]
Antimicrobial
activity
RGVSKKIMRTFLRRISK
K
NKCS-[FR]
Antimicrobial
activity
KILRGVSKKIMRTRLRRISKDILPGK
K
NKCS-[LP]
Antimicrobial
activity
KILRGVSKKIMRTFPRRISKDILTGKK
NKCS-[LP26]
Antimicrobial
activity
KILRGVSKKIMRTPRRISKDILTGKK
NK-2
NK-CS
NKCS-[AA]
NKCS-[FR]
NKCS-[LP]
NKCS-[LP26]
NKCS[MS]
NKCS-[14]
NKCS-[17]
NKCS-[20K]
NKCS-[RKK]
NKCS[15-27]
Specifically targeted antimicrobial
peptides
(STAMPs)
Repertoire of
Antibiotics
Microorganisms
including normal
flora
CSP
CS
P
Secondary infections
AMP
AM
P
S.mutans
Randal Eckert et. al.,
2006
Applications of AMP
Innate immunity
FeMetabolism
Food
preservation
AMP
Mitogens
Therapeutic
potential
Signal transduction
Therapeutic potential
Mode of
use
Peptide Company Application stage
Topical
Pexigana Magainin
n
Diabetic foot
ulcers
Completed
phase III
Topical
MBI-594
Micrologix
Acne
Phase II
Oral
IB-367
Intrabiotics Mucositis
Systemic
BPI
Xoma
Phase III
Meningococca Phase III
l menigitis
Zasloff et. al., 2002
AMP and Fe metabolism
Role of AMPs in Fe metabolism
Food preservation
peptide Structur
e
Sourc
e
Mechanism
of action
Target
PR-39
Pro and Arg
rich
mammal
s
Interfere with
DNA synthesis
S. Typhimurium
Sphenisci
n
Defensin like
Avian
Protamin
e
Arg rich
Fish
Distrupt
cytoplamic
memb
L.Monocytogene
s
Magainins
Helical
Xenopus
laevis
Pore formation
Food related
pathogen
Gram +ve &-ve
Tali Rydlo et. al., 2006
Anti-tumor activity
Tumor
cells
Normal cells
Difference in membrane
contents
High succeptibilty of tumor cells to
AMPs
Anti-tumor activity
Wojciech Kamysz et. al., 2003
High concentration
•Tumor cell lysis
•Lysis of microbes
•Stimulation of
keratinocyte growth
•Inhibition of protein
kinase C
•Stimulation of
cytokine production
•Stimulation of
adheshion molecule
expression
Low
concentration
Wojciech Kamysz et. al., 2003
CONCLUSION
 AMPs are multifunctional peptides
 These are having a wide spectrum of biological
activities
 Based on natural AMPs, synthetic analogs can be
developed
 These can be developed as Probiotic antibiotics