Understanding the Biophysical Interaction of LTX-315 with Tumoral Model Membranes

Abstract

Host defense peptides are found primarily as natural antimicrobial agents among all lifeforms. These peptides and their synthetic derivatives have been extensively studied for their potential use as therapeutic agents. The most accepted mechanism of action of these peptides is related to a nonspecific mechanism associated with their interaction with the negatively charged groups present in membranes, inducing bilayer destabilization and cell death through several routes. Among the most recently reported peptides, LTX-315 has emerged as an important oncolytic peptide that is currently in several clinical trials against different cancer types. However, there is a lack of biophysical studies regarding LTX-315 and its interaction with membranes. This research focuses primarily on the understanding of the molecular bases of LTX-315′s interaction with eukaryotic lipids, based on two artificial systems representative of non-tumoral and tumoral membranes. Additionally, the interaction with individual lipids was studied by differential scanning calorimetry and Fourier-transformed infrared spectroscopy. The results showed a strong interaction of LTX-315 with the negatively charged phosphatidylserine. The results are important for understanding and facilitating the design and development of improved peptides with anticancer activity.

Biophysical Insights into the Antitumoral Activity of Crotalicidin against Breast Cancer Model Membranes

“…The thermogram of the pure SM shows a broad gel-to-liquid-crystalline transition centered at 39.7 • C with ∆H = 40.2 kJ mol −1 . This result is in accordance with previous reports [22]. The incubation of the SM liposomes with the Ctn evokes profound changes in the DSC thermograms, indicating that the peptide exerts a destabilizing effect on the SM vesicles in a concentration-dependent manner by inducing phase separation, broadening the transition peak, and decreasing the enthalpy to 36.15 kJ mol −1 at the highest evaluated concentration.…”

Study of the Membrane Activity of the Synthetic Peptide ∆M3 Against Extended-Spectrum β-lactamase Escherichia coli Isolates

“…Another recognized peptide LTX-315, known as Oncopore™, a synthetic oncolytic peptide active in several cancer cell lines, has also been shown to be structureless in aqueous solution and model membranes made of 100% PC, 70/30% PC/PS, and 50% v/v TFE by circular dichroism (Koo et al 2022 ). Our previous work with infrared spectroscopy also demonstrated the described outcome using tumoral and non-tumoral model membranes (Klaiss-Luna et al 2023 ).…”

Study of the Membrane Activity of the Synthetic Peptide ∆M3 against Extended-Spectrum β-Lactamase Escherichia coli Isolates

“…LTX-315, known as Oncopore TM , a synthetic oncolytic peptide active in several cancer cell lines, has also been shown to be structureless in aqueous solution and model membranes made of 100% PC, 70/30 % PC/PS, and 50% v/v TFE by circular dichroism (20). Our previous work with infrared spectroscopy also demonstrated the described outcome using tumoral and non-tumoral model membranes (19).…”