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Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle : mechanistic insights into outer-membrane permeabilization and endotoxin neutralization

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle : mechanistic insights into outer-membrane permeabilization and endotoxin neutralization
นักวิจัย : Saravanan, Rathi , Mohanram, Harini , Joshi, Mangesh , Domadia, Prerna N. , Torres, Jaume , Ruedl, Christiane , Bhattacharjya, Surajit
คำค้น : DRNTU::Science::Biological sciences
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2555
อ้างอิง : Saravanan, R., Mohanram, H., Joshi, M., Domadia, P. N., Torres, J., Ruedl, C.,& Bhattacharjya, S. (2012). Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle: Mechanistic insights into outer-membrane permeabilization and endotoxin neutralization. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1818(7), 1613-1624. , 0005-2736 , http://hdl.handle.net/10220/12689 , http://dx.doi.org/10.1016/j.bbamem.2012.03.015
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Biochimica et Biophysica Acta (BBA) - biomembranes
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Tachyplesin-1, a disulfide stabilized β-hairpin antimicrobial peptide, can be found at the hemocytes of horse shoe crab Tachypleus tridentatus. A cysteine deleted linear analog of tachyplesin-1 or CDT (KWFRVYRGIYRRR-NH2) contains a broad spectrum of bactericidal activity with a reduced hemolytic property. The bactericidal activity of CDT stems from selective interactions with the negatively charged lipids including LPS. In this work, CDT–LPS interactions were investigated using NMR spectroscopy, optical spectroscopy and functional assays. We found that CDT neutralized LPS and disrupted permeability barrier of the outer membrane. Zeta potential and ITC studies demonstrated charge compensation and hydrophobic interactions of CDT with the LPS-outer membrane, respectively. Secondary structure of the peptide was probed by CD and FT-IR experiments indicating β-strands and/or β-turn conformations in the LPS micelle. An ensemble of structures, determined in LPS micelle by NMR, revealed a β-hairpin like topology of the CDT peptide that was typified by an extended cationic surface and a relatively shorter segment of hydrophobic region. Interestingly, at the non-polar face, residue R11 was found to be in a close proximity to the indole ring of W2, suggesting a cation–π type interactions. Further, saturation transfer difference (STD) NMR studies established intimate contacts among the aromatic and cationic residues of CDT with the LPS micelle. Fluorescence and dynamic light scattering experiments demonstrated that CDT imparted structural destabilization to the aggregated states of LPS. Collectively, atomic resolution structure and interactions of CDT with the outer membrane-LPS could be exploited for developing potent broad spectrum antimicrobial and anti-sepsis agents.

บรรณานุกรม :
Saravanan, Rathi , Mohanram, Harini , Joshi, Mangesh , Domadia, Prerna N. , Torres, Jaume , Ruedl, Christiane , Bhattacharjya, Surajit . (2555). Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle : mechanistic insights into outer-membrane permeabilization and endotoxin neutralization.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Saravanan, Rathi , Mohanram, Harini , Joshi, Mangesh , Domadia, Prerna N. , Torres, Jaume , Ruedl, Christiane , Bhattacharjya, Surajit . 2555. "Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle : mechanistic insights into outer-membrane permeabilization and endotoxin neutralization".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Saravanan, Rathi , Mohanram, Harini , Joshi, Mangesh , Domadia, Prerna N. , Torres, Jaume , Ruedl, Christiane , Bhattacharjya, Surajit . "Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle : mechanistic insights into outer-membrane permeabilization and endotoxin neutralization."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2555. Print.
Saravanan, Rathi , Mohanram, Harini , Joshi, Mangesh , Domadia, Prerna N. , Torres, Jaume , Ruedl, Christiane , Bhattacharjya, Surajit . Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle : mechanistic insights into outer-membrane permeabilization and endotoxin neutralization. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2555.