First slide

Research Interests

STRUCTURE - FUNCTION CORRELATIONS IN PEPTIDE ANTIBIOTICS : Our research has been directed towards structure-function correlations in antibacterial peptides with the objectives of (i) delineating regions that could be important for activity and (ii) designing peptides ~15 residues or less that would have selective antimicrobial activity. Our results indicate that it is possible design membrane-active peptides with selective activity against bacteria and have therapeutic potential. INTRACELLULAR SORTING OF PROTEINS: multiple palmitoylation of cellular proteins controls many important cellular events. We have shown that peptides containing palmitoylation sites could serve as useful models for understanding the role of this intriguing modification in cell biology. SELF-ASSEMBLY PROCESS IN PEPTIDES AND PROTEINS :Our research in this area has shown that self-assembled structures of peptides with varying morphologies and electrical properties can be obtained by judicious choice of solvents for dissolution and surfaces for deposition.

Selected Publications

Sitaram, N., and Nagaraj, R. (1999) Interaction of antimicrobial peptides with biological and model membranes: structural and charge requirements for activity. Biochim Biophys Acta 1462, 29-54.Mandal, M., Jagannadham, M. V., and Nagaraj, R. (2002) Antibacterial activities and conformations of bovine beta-defensin BNBD-12 and analogs:structural and disulfide bridge requirements for activity. Peptides 23, 413-418.

Pallavi, B., and Nagaraj, R. (2003) Palmitoylated peptides from the cysteine- rich domain of SNAP-23 cause membrane fusion depending on peptide length, position of cysteines, and extent of palmitoylation. J Biol Chem 278, 12737-12744.

Sowmya, B. L., Jagannadham, M. V., and Nagaraj, R. (2006) Interaction of synthetic peptides corresponding to the scaffolding domain of Caveolin-3 with model membranes. Biopolymers 84, 615-624.

Chaudhary, N., Singh, S., and Nagaraj, R. (2008) Organic solvent mediated self-association of an amyloid forming peptide from beta(2)-microglobulin: An atomic force microscopy study. Biopolymers 90, 783-791.

Education & Experiance

P.G: Chemistry ; IIT Bombay ; 1975
Ph.D: Stereochemically constrained amino acids ; IISc Bangalore ; 1980

Publications

TitleJournalYear
Impact on the replacement of Phe by Trp in a short fragment of Abeta amyloid peptide on the formation of fibrils. J Pept Sci 17, 115-123 2011
Self-assembly of short amyloidogenic peptides at the air-water interface. J Colloid Interface Sci 360, 139-147 2011
Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease. J Biosci In Press 2011
A Molecular Dynamics Study of Human Defensins HBD-1 and HNP-3 in Water. J Biomolstr Dynam 27, 541-550 2010
Characterization of Chemical Modification of Tryptophan by Matrix-Assisted Laser Desorption/ Ionization Mass Spectrometry. Protein & Peptide Lett 17, 168-171 2010
Determinants of membrane association in the SH4 domain of Fyn: Roles of N-terminus myristoylation and side-chain thioacylation. Biochim Biophys Acta. 1798,1854-1863 2010
Antifungal activities of human beta- defensins HBD-1 to HBD-3 and their C-terminal analogs Phd1 to Phd3. Antimicrob Agents Chemother53,256-260 2009
Peptides: Isolation, production, and use in India. Biotechnol J.4, 329-334. 2009
Hen lysozyme amyloid fibrils induce aggregation of erythrocytes and lipid vesicles. Mol Cell Biochem 328,209-215. 2009
Morphology of self-assembled structures formed by short peptides from the amyloidogenic protein tau depends on the solvent in which the peptides are dissolved. J Pept Sci 15, 675-684 2009
Interaction of 18-residue peptides derived from amphipathic helical segments of globular proteins with model membranes. J Biosci 34, 239-50 2009
Detecting the Site of Phosphorylation in Phosphopeptides Without Loss ofPhosphate Group Using MALDI TOFMass Spectrometry. Analytical Chemistry Insights 3, 21-29. 2008
Design, synthesis, conformational and membrane ion transport studies of proline-adamantane hybrid cyclic depsipeptides. Biopolymers 89, 471-478 2008
Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1-3 with phospholipids at the air-water interface and inner membrane of E. coli. Peptides 29, 7-14 2008
Synthesis, conformational analysis and biological studies of cyclic cationic antimicrobial peptides containing sugar amino acids. J Org Chem 73, 8731-44 2008
Organic solvent mediated self- association of an amyloid forming peptide from beta(2)-microglobulin: An atomic force microscopy study. Biopolymers 90, 783-791. 2008
Diphenic Acid as a General Conformational Lock in the Design of Bihelical Structures Chemistry, 13(15): 4253-4263 2007
Antibacterial activities of synthetic peptides corresponding to the carboxy-terminal region of human beta-defensins 1-3 Peptides, 27(11): 2607-2613 2006
Antibacterial activity of linear peptides spanning the carboxy-terminal beta-sheet domain of arthropod defensins Peptides, 27(11): 2614-2623 2006
Interaction of synthetic peptides corresponding to the scaffolding domain of Caveolin-3 with model membranes Biopolymers, 84(6): 615-624 2006
Conformation and activity of delta-lysin and its analogs Peptides., 26(2): 217-25 2005
Amphipathic alpha-helices in proteins: results from analysis of protein structures Proteins., 59(4): 791-801 2005
Conformation of gramicidin a in water: inference from analysis of hydrogen/deuterium exchange behavior by matrix assisted laser desorption ionization mass spectrometry Biopolymers., 80(5): 708-13 2005
Interaction of a pseudosubstrate peptide of protein kinase C and its myristoylated form with lipid vesicles: only the myristoylated form translocates into the lipid bilayer Biochim Biophys Acta., 1713(2): 73-82 2005
Detection of peptides covalently modified with multiple fatty acids by MALDI-TOF mass spectrometry J Pept Res., 66(2): 94-100 2005
Antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines Antimicrob Agents Chemother., 49(11): 4561-6 2005
Bacterial lipid modification of proteins for novel protein engineering applications Protein Eng Des Sel., 17(10): 721-9 2004
Palmitoylated peptides from the cysteine-rich domain of SNAP-23 cause membrane fusion depending on peptide length, position of cysteines, and extent of palmitoylation J Biol Chem., 278(15): 12737-44 2003
Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides Mol Biochem Parasitol., 127(1): 23-35 2003
Cyclic homooligomers of furanoid sugar amino acids J Org Chem., 68(16): 6257-63 2003
Single disulfide and linear analogues corresponding to the carboxy-terminal segment of bovine beta-defensin-2: effects of introducing the beta-hairpin nucleating sequence d-pro-gly on antibacterial ac Biochemistry., 42(31): 9307-15 2003
Indolicidin, a 13-residue basic antimicrobial peptide rich in tryptophan and proline, interacts with Ca(2+)-calmodulin Biochem Biophys Res Commun., 309(4): 879-84 2003
Antibacterial activities and conformations of bovine beta-defensin BNBD-12 and analogs:structural and disulfide bridge requirements for activity Peptides., 23(3): 413-8 2002
NMR study of cyclic peptides with renin inhibitor activity J Biochem Biophys Methods., 51(1): 27-45 2002
Host-defense antimicrobial peptides: importance of structure for activity Curr Pharm Des., 8(9): 727-42 2002
Antibacterial activities and conformations of synthetic alpha-defensin HNP-1 and analogs with one, two and three disulfide bridges J Pept Res., 59(3): 95-104 2002
The therapeutic potential of host-defense antimicrobial peptides Curr Drug Targets., 3(3): 259-67 2002
Structure-function relationship studies on the frog skin antimicrobial peptide tigerinin 1: design of analogs with improved activity and their action on clinical bacterial isolates Antimicrob Agents Chemother., 46(7): 2279-83 2002
Structure-function relationship studies on the frog skin antimicrobial peptide tigerinin 1: design of analogs with improved activity and their action on clinical bacterial isolates Antimicrob Agents Chemother., 46(7): 2279-83 2002
Subcellular localization and physiological consequences of introducing a mitochondrial matrix targeting signal sequence in bax and its mutants Exp Cell Res., 278(2): 198-208 2002
A synthetic strategy for ON-resin amino acid specific multiple fatty acid acylation of peptides Protein Pept Lett ., 9(5): 411-7 2002
Effects of deleting a tripeptide sequence observed in muscular dystrophy patients on the conformation of synthetic peptides corresponding to the scaffolding domain of caveolin-3 Biochem Biophys Res Commun., 298(2): 203-6 2002
Biological activities of retro and diastereo analogs of a 13-residue peptide with antimicrobial and hemolytic activities J Pept Res., 57(1): 59-67 2001
Effects of salt and denaturant on structure of the amino terminal alpha-helical segment of an antibacterial peptide dermaseptin and its binding to model membranes Indian J Biochem Biophys., 38(3): 142-8 2001
Immunobiology of a synthetic luteinizing hormone receptor peptide 21-41 J Androl., 22(6): 992-8 2001
Structure-function studies on the amphibian peptide brevinin 1E: translocating the cationic segment from the C-terminal end to a central position favors selective antibacterial activity J Pept Res., 58(5): 433-41 2001
Double-helical cyclic peptides: design, synthesis, and crystal structure of figure-eight mirror-image conformers of adamantane-constrained cystine-containing cyclic peptide cyclo (Adm-Cyst)(3) J Org Chem., 65(14: 4415-22 2000
Antibacterial and hemolytic activities of single tryptophan analogs of indolicidin Biochem Biophys Res Commun., 274(3): 714-6 2000
Solid-phase synthesis of a modified 13-residue seminalplasmin fragment on 1,6-hexanediol diacrylate-crosslinked polystyrene support Peptides., 21(6): 773-7 2000
Tigerinins: novel antimicrobial peptides from the Indian frog Rana tigerina J Biol Chem., 276(4): 2701-7 2000
Synthesis and conformational studies of peptidomimetics containing furanoid sugar amino acids and a sugar diacid J Org Chem., 5(22): 7710 2000

R Nagaraj

J C Bose Fellow

2589

nraj@ccmb.res.in

Ankeeta Guru

Project Assistant-II

Thushar Rajjan Moharana

Senior Research Fellow(Project)

Taniya Mary Binny

Junior Research Fellow (Project)