Antimicrobial, cytotoxic, and insulin‐releasing activities of the amphibian host‐defense peptide ocellatin‐3N and its L‐lysine‐substituted analogs

Abstract

The host-defense peptide ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH 2 ), first isolated from the Caribbean frog Leptodactylus nesiotus, inhibited growth of clinically relevant Gram-positive and Gram-negative bacteria as well as a strain of the major emerging yeast pathogen Candida parapsilosis. Increasing cationicity while maintaining amphipathicity by the substitution Asp 4 !Lys increased potency against the microorganisms by between 4-and 16-fold (MIC ≤3 μM) compared with the naturally occurring peptide. The substitution Ala 18 !Lys and the double substitution Asp 4 !Lys and Ala 18 !Lys had less effects on potency. The [D4K] analog also showed 2.5-to 4-fold greater cytotoxic potency against non-small-cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells (LC 50 values in the range of 12-20 μM) compared with ocellatin-3N but was less hemolytic to mouse erythrocytes. However, the peptide showed no selectivity for tumor-derived cells [LC 50 = 20 μM for human umbilical vein endothelial cells (HUVECs)]. Ocellatin-3N and [D4K]ocellatin-3N stimulated the release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥1 nM, and [A18K]ocellatin-3N, at concentrations ≥0.1 nM. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM, indicating that plasma membrane integrity had been preserved. The three peptides produced an increase in intracellular [Ca 2+ ] in BRIN-BD11 cells when incubated at a concentration of 1 μM. In view of its high insulinotropic potency and relatively low hemolytic activity, the [A18K] ocellatin analog may represent a template for the design of agents with therapeutic potential for the treatment of patients with type 2 diabetes.

First Report of Ocellatin-VT from the Skin Secretion of Leptodactylus vastus Lutz (Amphibia: Leptodactylidae)

“…When studying the ocellatins (LB1, LB2, and F1) from L. labyrinthicus, Gusmão et al [22] showed activity against E. coli, and specifically, ocellatin-F1 was active on S. aureus. Colon et al [28] isolated ocellatin-3N from Leptodactylus nesiotus and reported its ability to inhibit the growth of A. baumannii and P. aeruginosa.…”

Exploration of the Antibacterial and Anti-Inflammatory Activity of a Novel Antimicrobial Peptide Brevinin-1BW

“…Additionally, antimicrobial peptides cause minimal damage to host cells and enhance host immune function, aiding in disease recovery and maintaining physiological functions [28,29]. Furthermore, antimicrobial peptides have potential effects such as anti-inflammatory properties [30,31], anticancer properties [32], and insulin-release promotion [33][34][35], indicating their potential as antibiotic alternatives. However, compared to antibiotics, the pharmacological properties of antimicrobial peptides are still under investigation, and their clinical applications are in the early stages, necessitating further research and development for widespread use.…”