2. 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

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

4.  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 Cont…

5. Structure and Classification of AMPs PREPROPEPTIDE Signal peptidaseElastase 29-30 residues 98-114 residues 12- 50 residues PEPTIDEPRE

6. 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

7. 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….

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

10. Amino acid sequence of NK- Lysin

11. KILRGVCKKIMRTFLRRISKDILTGK K 151010 1515 2025 Sequence of NK-2 Antimicrobial activity

12. NK-CS KLLRGVSKKIMRTFLRRISKDILTGKK Antimicrobial activity

13. NKCS-[MS] KILRGVSKKISRTFLRRISKDILTGKK Antimicrobial activity

14. KLLRGVSKKIMRTFLRRISKKDILTGKK NKCS-shortened analogues

15. KILRGVSKKIMRTFLRRISK K NKCS- [20K] Antimicrobial activity

16. RGVSKKIMRTFLRRISK K NKCS-[RKK] Antimicrobial activity

17. NKCS-[FR] KILRGVSKKIMRTRLRRISKDILPGK K Antimicrobial activity

18. KILRGVSKKIMRTFPRRISKDILTGKK NKCS-[LP] Antimicrobial activity

19. KILRGVSKKIMRTPRRISKDILTGKK NKCS-[LP26] Antimicrobial activity

20. 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]

21. 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

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

23. 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

24. AMP and Fe metabolism

25. Role of AMPs in Fe metabolism

26. 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

27. Tumor cells Normal cells Difference in membrane contents High succeptibilty of tumor cells to AMPs Anti-tumor activity Wojciech Kamysz et. al., 2003

28. 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

29. 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