Synthesis and Anti-microbial Activity of Novel Phosphatidylethanolamine-N-amino Acid Derivatives.

The study involved synthesis of five novel amino acid derivatives of phosphatidylethanolamine isolated from egg yolk lecithin employing a three step procedure i) N-protection of L-amino acids with BOC anhydride in alkaline medium ii) condensation of - CO2H group of N-protected amino acid with free -NH2 of PE by a peptide linkage and iii) deprotection of N-protected group of amino acids to obtain phosphatidylethanolamine-N-amino acid derivatives in 60-75% yield. The five L-amino acids used were L glycine, L-valine, L-leucine, L-isoleucine and L-phenylalanine. The amino acid derivatives were screened for anti-baterial activity against B. subtilis, S. aureus, P. aeroginosa and E. coli taking Streptomycin as reference compound and anti-fungal activity against C. albicans, S. cervisiae, A. niger taking AmphotericinB as reference compound. All the amino acid derivatives exhibited extraordinary anti-bacterial activities about 3 folds or comparable to Streptomycin and moderate or no anti-fungal activity against Amphotericin-B.

[1]  S. S. Kanwar,et al.  Lipopeptides as the Antifungal and Antibacterial Agents: Applications in Food Safety and Therapeutics , 2015, BioMed research international.

[2]  H. Hansen,et al.  N-acylation of phosphatidylethanolamine and its biological functions in mammals. , 2013, Biochimica et biophysica acta.

[3]  R. Prasad,et al.  A Simple Enzymatic Approach for Selective Acetylation of Phosphatidylethanolamine , 2013 .

[4]  D. Mercer,et al.  Production and Evaluation of an Antimicrobial Peptide-Containing Wafer Formulation for Topical Application , 2013, Current Microbiology.

[5]  R. B. Merrifield,et al.  Antibacterial peptides designed as analogs or hybrids of cecropins and melittin. , 2009, International journal of peptide and protein research.

[6]  R. Hancock,et al.  Mode of action of the new antibiotic for Gram-positive pathogens daptomycin: comparison with cationic antimicrobial peptides and lipopeptides. , 2006, Biochimica et biophysica acta.

[7]  H. Hansen,et al.  N-acyl phosphatidylethanolamines affect the lateral distribution of cholesterol in membranes. , 2005, Biochimica et biophysica acta.

[8]  C. Aranha,et al.  Antimicrobial peptides: premises and promises. , 2004, International journal of antimicrobial agents.

[9]  Ronald J A Wanders,et al.  Functions and biosynthesis of plasmalogens in health and disease. , 2004, Biochimica et biophysica acta.

[10]  Marianne Terrot,et al.  Combinatorial lead optimization of [1,2]-diamines based on ethambutol as potential antituberculosis preclinical candidates. , 2003, Journal of combinatorial chemistry.

[11]  K. Arnoldsson,et al.  Characterization of N-acylphosphatidylethanolamine and acylphosphatidylglycerol in oats , 2001, Lipids.

[12]  C. Lingwood,et al.  Enterohemorrhagic Escherichia coliInduces Apoptosis Which Augments Bacterial Binding and Phosphatidylethanolamine Exposure on the Plasma Membrane Outer Leaflet , 2000, Infection and Immunity.

[13]  D. Philpott,et al.  Phosphatidylethanolamine recognition promotes enteropathogenic E. coli and enterohemorrhagic E. coli host cell attachment. , 1999, Microbial pathogenesis.

[14]  P. Vreken,et al.  Plasmalogen phospholipids are involved in HDL-mediated cholesterol efflux: insights from investigations with plasmalogen-deficient cells. , 1998, Biochemical and biophysical research communications.

[15]  R. Hancock,et al.  Cationic peptides: a new source of antibiotics. , 1998, Trends in biotechnology.

[16]  R. Epand,et al.  Effect of N-acyl-phosphatidylethanolamine on the Membrane Fusion Between Sendai Virus and Liposome , 1997, Bioscience reports.

[17]  R. Hancock,et al.  Peptide antibiotics , 1997, The Lancet.

[18]  F. Rosell,et al.  Structural organization of N-acyl derivatives of egg phosphatidylethanolamine into bilayers: polymorphic and thermotropic studies , 1996 .

[19]  L. Franzoni,et al.  The chemical synthesis of N-[1-(2-naphthol)]-phosphatidylethanolamine, a fluorescent phospholipid for excited-state proton transfer studies. , 1992, Chemistry and physics of lipids.

[20]  M. Zasloff,et al.  Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[21]  R. Glew,et al.  Comparison of N-acyl phosphatidylethanolamines with different N-acyl groups as activators of glucocerebrosidase in various forms of Gaucher's disease. , 1985, Archives of biochemistry and biophysics.

[22]  S. Kinsky,et al.  Antibody formation in response to liposomal model membranes sensitized with N-substituted phosphatidylethanolamine derivatives. , 1974, Biochemistry.

[23]  R. Aneja,et al.  N-Acylphosphatidylethanolamines: occurrence in nature, structure and stereochemistry. , 1969, Biochemical and biophysical research communications.

[24]  R. Bomstein.  A new class of phosphatides isolated from soft wheat flour. , 1965, Biochemical and biophysical research communications.

[25]  E. M. Linday.  PRACTICAL INTRODUCTION TO MICROBIOLOGY , 1962, The Ulster Medical Journal.

[26]  H. Mangold.  Thin-layer chromatography of lipids , 1961 .

[27]  H. Schmid,et al.  N-acylated glycerophospholipids and their derivatives. , 1990, Progress in lipid research.