Nyquistin

Nyquistin is a synthetic antimicrobial peptide developed by researchers aiming to enhance membrane-targeting activity against pathogenic bacteria. Named after the Nyquist principle, the peptide is designed to combine high positive charge with hydrophobic residues to promote interaction with negatively charged microbial membranes while limiting off-target effects on human cells.

Nyquistin is a short, typically 12 to 14 amino acids in length, rich in lysine and arginine and capable of adopting an amphipathic alpha-helix in lipid environments. Variants of Nyquistin employ structural features such as cyclization or the inclusion of D-amino acids to improve proteolytic stability and functional potency. In preclinical studies, Nyquistin shows rapid bactericidal activity, often within minutes of exposure, and demonstrates activity against several Gram-positive pathogens; activity against Gram-negative organisms varies and can be limited by outer-membrane barriers.

The proposed mechanism involves electrostatic attraction to the bacterial surface followed by disruption of the lipid bilayer, leading to depolarization and pore formation. This membrane-targeting mode reduces the likelihood of cross-resistance with conventional antibiotics, though resistance mechanisms that alter membrane composition have been observed in some models.

Synthesis is typically accomplished by solid-phase peptide synthesis, with optional cyclization or incorporation of non-natural residues to enhance stability and selectivity. In vitro assays report low cytotoxicity against mammalian cells at therapeutic concentrations, but comprehensive toxicity data are limited.

Current status places Nyquistin in the preclinical research phase. Investigations focus on spectrum expansion, delivery methods for topical use, and potential applications in medical-device coatings. Regulatory approval has not been pursued for clinical use.