EMERGING TRENDS IN ANTIMICROBIAL PEPTIDES DEVELOPMENT AND APPLICATIONS JITENDER MEHLA & Dr.R.A.SIDDIQUE RESEARCH SCHOLARS, ANIMAL BIOCHEMISTRY DIVISION.

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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

HOST INNATE IMMUNITY PATHOGENS DIFFERENT COMPONENTS ANTIMICROBIAL PEPTIDES WHAT ARE AMPs?

 Small peptides having app 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 Cont…

Structure and Classification of AMPs PREPROPEPTIDE Signal peptidaseElastase residues residues residues PEPTIDEPRE

CLASSEXAMPLESTRUCTUREORIGIN Anionic peptides DermicidinAsp & GluHuman Cationic peptides CecropinHelicalinsects LL37HelicalHuman Cationic peptides with specific amino acids PR 39Pro & arg rich Pig PropheninPro & PhePig IndolicidinTrp richcattle Classification of AMPs

Peptides that forms disulphide bridges Brevinins1-disulphide bridge Amphibians Tachyplesin2-disulphide bridges Horse shoe crab Defensins3-disulfide bridges Human NK-lysin3-disulfide bridges Pig DrosomycinMore than 3- disulfide bridges Fruitfly Fragmented peptides Lactoferricin14-42 a.acidsHuman Cont….

Transcriptional regulation of AMPs Taeil Kim et.al., 2005

Amino acid sequence of NK- Lysin

KILRGVCKKIMRTFLRRISKDILTGK K Sequence of NK-2 Antimicrobial activity

NK-CS KLLRGVSKKIMRTFLRRISKDILTGKK Antimicrobial activity

NKCS-[MS] KILRGVSKKISRTFLRRISKDILTGKK Antimicrobial activity

KLLRGVSKKIMRTFLRRISKKDILTGKK NKCS-shortened analogues

KILRGVSKKIMRTFLRRISK K NKCS- [20K] Antimicrobial activity

RGVSKKIMRTFLRRISK K NKCS-[RKK] Antimicrobial activity

NKCS-[FR] KILRGVSKKIMRTRLRRISKDILPGK K Antimicrobial activity

KILRGVSKKIMRTFPRRISKDILTGKK NKCS-[LP] Antimicrobial activity

KILRGVSKKIMRTPRRISKDILTGKK NKCS-[LP26] Antimicrobial activity

NK-2 NK-CS NKCS-[AA]NKCS-[FR]NKCS-[14]NKCS[15-27]NKCS[MS] NKCS-[LP] NKCS-[LP26] NKCS-[17] NKCS-[RKK] NKCS-[20K]

Specifically targeted antimicrobial peptides (STAMPs) Repertoire of Antibiotics Microorganisms including normal flora Secondary infections CSPAMP CS P AM P S.mutans Randal Eckert et. al., 2006

Applications of AMP AMP Innate immunity Food preservation Therapeutic potential Signal transduction Mitogens Fe- Metabolism

Mode of use PeptideCompanyApplicationstage TopicalPexigana n MagaininDiabetic foot ulcers Completed phase III TopicalMBI-594MicrologixAcnePhase II OralIB-367IntrabioticsMucositisPhase III SystemicBPIXomaMeningococca l menigitis Phase III Therapeutic potential Zasloff et. al., 2002

AMP and Fe metabolism

Role of AMPs in Fe metabolism

peptideStructur e Sourc e Mechanism of action Target PR-39Pro and Arg rich mammal s Interfere with DNA synthesis S. Typhimurium Sphenisci n Defensin - like AvianGram +ve &-ve Protamin e Arg richFishDistrupt cytoplamic memb L.Monocytogene s MagaininsHelicalXenopus laevis Pore formationFood related pathogen Food preservation Tali Rydlo et. al., 2006

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 Low 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 Spectrum of biological activity of AMPs 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

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