thetadefensins

Thetadefensins, also known as theta-defensins, are a class of defensins, small, cysteine-rich antimicrobial peptides that participate in innate immune defense. They are unique among defensins for their head-to-tail cyclized backbone, which arises from covalent linkage between the peptide's N- and C- termini. Thetadefensins have been identified in several species of non-human primates, most notably rhesus macaques and baboons, but not in humans.

Structure and chemistry: Thetadefensins are very short, typically around 18 amino acids, and contain six cysteine residues that form three disulfide bonds. Their cyclic topology and disulfide framework confer notable stability to proteolysis and a compact, rigid fold that supports their antimicrobial activity.

Biological activity: Thetadefensins exhibit broad-spectrum antimicrobial effects in vitro, including activity against bacteria, fungi, and enveloped viruses. In several studies, theta-defensin peptides from rhesus macaques have demonstrated potent activity against HIV-1 and other viral agents, often through interactions with viral particles or host cell surfaces and by disrupting membranes.

Genetics and distribution: In humans, thetadefensin genes are not known to be expressed as functional peptides; the locus is considered nonfunctional or absent in the human genome. By contrast, thetadefensin genes are expressed in neutrophils and mucosal tissues of some non-human primates, where they are processed to yield cyclic mature peptides.

Research and potential applications: The unusual stability and broad activity of thetadefensins have made them objects of interest for antimicrobial and antiviral research. Synthetic analogs have been studied to assess therapeutic potential, though challenges include ensuring safety, specificity, and effective in vivo delivery.