期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 15, 页码 10830-10840出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.451047
关键词
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资金
- Australian Research Council [DP0984390, DE120103152]
- University of Queensland
- National Health and Medical Research Council [APP631420, APP1026501]
- Queensland Government
- Australian Research Council [DE120103152] Funding Source: Australian Research Council
theta-Defensins are ribosomally synthesized cyclic peptides found in the leukocytes of some primate species and have promising applications as antimicrobial agents and scaffolds for peptide drugs. The cyclic cystine ladder motif, comprising a cyclic peptide backbone and three parallel disulfide bonds, is characteristic of theta-defensins. In this study, we explore the role of the cyclic peptide backbone and cystine ladder in the structure, stability, and activity of theta-defensins. theta-Defensin analogues with different numbers and combinations of disulfide bonds were synthesized and characterized in terms of their NMR solution structures, serum and thermal stabilities, and their antibacterial and membrane-binding activities. Whereas the structures and stabilities of the peptides were primarily dependent on the number and position of the disulfide bonds, their antibacterial and membrane-binding properties were dependent on the cyclic backbone. The results provide insights into the mechanism of action of theta-defensins and illustrate the potential of theta-defensin analogues as scaffolds for peptide drug design.
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