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Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility
นักวิจัย : Saravanan, Rathi , Li, Xiang , Lim, Kaiyang , Mohanram, Harini , Peng, Li , Mishra, Biswajit , Basu, Anindya , Lee, Jong-Min , Bhattacharjya, Surajit , Leong, Susanna Su Jan
คำค้น : DRNTU::Engineering::Bioengineering.
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2556
อ้างอิง : Saravanan, R., Li, X., Lim, K., Mohanram, H., Peng, L., Mishra, B., et al. (2014). Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility. Biotechnology and Bioengineering, 111(1), 37-49. , 0006-3592 , http://hdl.handle.net/10220/19188 , http://dx.doi.org/10.1002/bit.25003
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Biotechnology and bioengineering
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Antimicrobial peptides (AMPs) kill microbes by non-specific membrane permeabilization, making them ideal templates for designing novel peptide-based antibiotics that can combat multi-drug resistant pathogens. For maximum efficacy in vivo and in vitro, AMPs must be biocompatible, salt-tolerant and possess broad-spectrum antimicrobial activity. These attributes can be obtained by rational design of peptides guided by good understanding of peptide structure-function. Toward this end, this study investigates the influence of charge and hydrophobicity on the activity of tryptophan and arginine rich decamer peptides engineered from a salt resistant human β-defensin-28 variant. Mechanistic investigations of the decamers with detergents mimicking the composition of bacterial and mammalian membrane, reveal a correlation between improved antibacterial activity and the increase in tryptophan and positive residue content, while keeping hemolysis low. The potent antimicrobial activity and high cell membrane selective behavior of the two most active decamers, D5 and D6, are attributed to an optimum peptide charge to hydrophobic ratio bestowed by systematic arginine and tryptophan substitution. D5 and D6 show surface localization behavior with binding constants of 1.86 × 108 and 2.6 × 108 M−1, respectively, as determined by isothermal calorimetry measurements. NMR derived structures of D5 and D6 in SDS detergent micelles revealed proximity of Trp and Arg residues in an extended structural scaffold. Such potential cation–π interactions may be critical in cell permeabilization of the AMPs. The fundamental characterization of the engineered decamers provided in this study improves the understanding of structure–activity relationship of short arginine tryptophan rich AMPs, which will pave the way for future de novo design of potent AMPs for therapeutic and biomedical applications.

บรรณานุกรม :
Saravanan, Rathi , Li, Xiang , Lim, Kaiyang , Mohanram, Harini , Peng, Li , Mishra, Biswajit , Basu, Anindya , Lee, Jong-Min , Bhattacharjya, Surajit , Leong, Susanna Su Jan . (2556). Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Saravanan, Rathi , Li, Xiang , Lim, Kaiyang , Mohanram, Harini , Peng, Li , Mishra, Biswajit , Basu, Anindya , Lee, Jong-Min , Bhattacharjya, Surajit , Leong, Susanna Su Jan . 2556. "Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Saravanan, Rathi , Li, Xiang , Lim, Kaiyang , Mohanram, Harini , Peng, Li , Mishra, Biswajit , Basu, Anindya , Lee, Jong-Min , Bhattacharjya, Surajit , Leong, Susanna Su Jan . "Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2556. Print.
Saravanan, Rathi , Li, Xiang , Lim, Kaiyang , Mohanram, Harini , Peng, Li , Mishra, Biswajit , Basu, Anindya , Lee, Jong-Min , Bhattacharjya, Surajit , Leong, Susanna Su Jan . Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt-resistance, and biocompatibility. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2556.