Cole Alexander M, Lehrer Robert I
David Geffen School of Medicine at UCLA, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Los Angeles, CA 90095, USA.
Curr Pharm Des. 2003;9(18):1463-73. doi: 10.2174/1381612033454667.
Over 80 different alpha-defensin or beta-defensin peptides are expressed by the leukocytes and epithelial cells of birds and mammals. Although their broad spectrum antimicrobial properties makes them candidates for therapeutic development, technical limitations related to their size (typically 30-45 residues) and complex structure have impeded such development. The minidefensins covered in this review are antimicrobial peptides with 16-18 residues, approximately half the number found in alpha-defensins. The theta-defensins are evolutionarily related toalpha- and beta-defensins, but other minidefensins probably arose independently. Like alpha- or beta-defensins, minidefensin molecules have a net positive charge and a largely beta-sheet structure that is stabilized by intramolecular disulfide bonds. Whereas alpha-defensins are found only in mammals and theta-defensins only in nonhuman primates, the other minidefensins come from widely divergent species, including horseshoe crabs, spiders, and pigs. Several alpha-defensins and minidefensins are effective inhibitors of HIV-1 infection in vitro, and recent evidence implicates alpha-defensins in resistance to HIV-1 progression in vivo. This review compares defensins and minidefensins with respect to their activity against HIV-1. It pays special attention to retrocyclins - the ancestral theta-defensins of humans, and their extant counterparts in rhesus monkeys. In addition to describing critical elements of their structure and unusual mode of formation, we will venture some predictions about using theta-defensins as antiviral agents.
鸟类和哺乳动物的白细胞及上皮细胞可表达80多种不同的α-防御素或β-防御素肽。尽管它们具有广谱抗菌特性，使其成为治疗药物开发的候选对象，但由于其大小（通常为30 - 45个残基）和复杂结构相关的技术限制，阻碍了此类开发。本综述中涵盖的微型防御素是具有16 - 18个残基的抗菌肽，大约是α-防御素残基数量的一半。θ-防御素在进化上与α-和β-防御素相关，但其他微型防御素可能是独立产生的。与α-或β-防御素一样，微型防御素分子带有净正电荷，且具有主要由分子内二硫键稳定的β-折叠结构。α-防御素仅在哺乳动物中发现，θ-防御素仅在非人类灵长类动物中发现，而其他微型防御素则来自广泛不同的物种，包括鲎、蜘蛛和猪。几种α-防御素和微型防御素在体外是HIV - 1感染的有效抑制剂，最近的证据表明α-防御素在体内对HIV - 1进展具有抗性。本综述比较了防御素和微型防御素对HIV - 1的活性。特别关注逆转环素——人类的祖先θ-防御素及其在恒河猴中的现存对应物。除了描述它们结构的关键要素和不寻常的形成方式外，我们还将对使用θ-防御素作为抗病毒药物进行一些预测。
