PEGylation of the antimicrobial peptide LyeTx I-b maintains structure-related biological properties and improves selectivity

• DOI: 10.3389/fmolb.2022.1001508
• Publication Date: 2022-10-13T16:01:22Z
• Authors: Júlio César Morei...; Lucas Raposo Carv...; Amanda Neves de S...; Guilherme Carneiro; Paula Prazeres Ma...; Luiz Macêdo Farias; Natália Rocha Gui...; Rodrigo Moreira V...; Jarbas Magalhães ...; Maria Elena de Lima
• Keywords: PEGylation

The biological activity of antimicrobial peptides and proteins is closely related to their structural aspects sensitive certain post-translational modifications such as glycosylation, lipidation PEGylation. However, PEGylation protein peptide drugs has expanded in recent years due the reduction toxicity. Due size, process can either preserve or compromise overall structure these biopolymers properties. LyeTx I-b cys was synthesized by Fmoc strategy coupled polyethylene glycol 2.0 kDa. conjugates were purified HPLC characterized MALDI-ToF-MS analysis. Microbiological assays with I-bPEG performed against Staphylococcus aureus (ATCC 33591) Escherichia coli 25922) liquid medium. MIC values 1.0 µM for 8.0 4.0 observed S. E. , respectively. (LyeTx I-bPEG) decreased cytotoxicity determined MTT method VERO cells compared non-PEGylated peptide. In addition, biophysical studies evaluate effects on nature peptide-membrane interactions. Surface Plasmon Resonance experiments showed that binds anionic membranes an association constant twice higher than PEGylated form. three-dimensional NMR structures structure, hydrodynamic diameter zeta potential POPC:POPG vesicles similar upon addition both peptides. mPEG-MAL conjugation gave epimers, it, together I-bPEG, clear α-helical profiles. While no significant change amphipathicity I-b, found have a slightly less separation between hydrophilic hydrophobic faces. conformational freedom suggests does not cause changes. Overall, our indicate alter mode interaction maintains while minimizing tissue toxicity, which confirmed previous results obtained vivo . Interestingly, significantly improved proteolytic resistance trypsin proteinase K after