1. Synthesis and structure-activity relationship of beta-defensins, multi-functional peptides of the immune system
Enno Klüver, Knut Adermann, Axel Schulz J Pept Sci. 2006 Apr;12(4):243-57. doi: 10.1002/psc.749.
beta-defensins are a large family of multiple disulfide-bonded peptides occurring in mammals and birds. They play an important role in the innate immune system, directly killing microbial organisms. Recent research has demonstrated that beta-defensins are important for other biological functions beyond antimicrobial effects, including inhibition of viral infection, interaction with Toll-like receptors, chemotactic effects, and sperm function. The corresponding broad spectrum of activities makes this peptide class an important subject and tool in immunologic research. In this review, we summarize the current status of the routes to obtain synthetic beta-defensins, their major structural properties and structure-activity relationship.
2. Structural and functional characterization of hBD-1(Ser35), a peptide deduced from a DEFB1 polymorphism
Raffaella Circo, Barbara Skerlavaj, Renato Gennaro, Antonio Amoroso, Margherita Zanetti Biochem Biophys Res Commun. 2002 Apr 26;293(1):586-92. doi: 10.1016/S0006-291X(02)00267-X.
beta-Defensins are mammalian antimicrobial peptides that share a unique disulfide-bonding motif of six conserved cysteines. An intragenic polymorphism of the DEFB1 gene that changes a highly conserved Cys to Ser in the peptide coding region has recently been described. The deduced peptide cannot form three disulfide bonds, as one of the cysteines is unpaired. We have determined the cysteine connectivities of a corresponding synthetic hBD-1(Ser35) peptide, investigated the structure by circular dichroism spectroscopy, and assayed the in vitro antimicrobial activity. Despite a different arrangement of the disulfides, hBD-1(Ser35) proved as active as hBD-1 against the microorganisms tested. This activity likely depends on the ability of hBD-1(Ser35) to adopt an amphipathic conformation in hydrophobic environment, similar to the wild type peptide, as suggested by CD spectroscopy.
3. The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry
L Liu, C Zhao, H H Heng, T Ganz Genomics. 1997 Aug 1;43(3):316-20. doi: 10.1006/geno.1997.4801.
We cloned a novel human beta-defensin gene and determined its full-length cDNA sequence. The entire gene spanned more than 7 kb and included a large 6962-bp intron. The 362-bp cDNA encoded a prepropeptide that corresponded precisely to the recently identified human beta-defensin HBD-1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. By two-color fluorescence in situ hybridization on both metaphase chromosome and released chromatin fiber, HBD-1 gene (DEFB1 in HUGO/GDB nomenclature) mapped to chromosomal region 8p23.1-p23.2 in close proximity (within 100-150 kb) to the gene for the human neutrophil alpha-defensin HNP-1 (DEFA1). Thus, despite a complete lack of DNA sequence similarity and despite differences in their disulfide-pairing pattern, the alpha- and beta-families appear to have evolved from a common premammalian defensin gene.
