Caerin

The proline residue at position 15 of caerin 1.1 induces a kink between two amphipathic helices. This bent conformation allows the molecule to interact with curved membrane surfaces and is thought to facilitate insertion into the highly curved membranes of microvesicles and viral envelopes. The two helices act cooperatively to disrupt membrane integrity, explaining the broad-spectrum activity including against enveloped viruses.

Caerin 1.1 directly inactivates HIV virions by disrupting the viral lipid envelope, preventing cell entry. Unlike entry inhibitors targeting specific receptors, membrane disruption is a resistance-prone mechanism for the virus since envelope lipid composition is largely determined by the host cell. Studies have shown activity against cell-free virus at concentrations that spare human T-lymphocytes.

Caerin 1.1 and 1.9 inactivate HIV-1 in cell-free assays and prevent infection of CD4+ T-cells in vitro. Combination studies with caerin 1.9 and caerin 4.1 show enhanced anti-HIV activity compared to individual peptides. The mechanism of direct viral envelope disruption differs from current antiretroviral drug classes, suggesting potential for use in HIV prevention formulations (microbicides).

Caerin peptides selectively kill a range of human cancer cell lines including ovarian, cervical, breast, and prostate carcinomas. Mechanistic studies indicate apoptosis induction through mitochondrial pathway activation following membrane permeabilization. The selectivity for cancer versus normal cells involves the same phosphatidylserine-based discrimination observed for other frog skin AMPs.