Design of Membrane Active Peptides Considering Multi-Objective Optimization for Biomedical Application

Abstract

A multitude of membrane active peptides exists that divides into subclasses, such as cell penetrating peptides (CPPs) capable to enter eukaryotic cells or antimicrobial peptides (AMPs) able to interact with prokaryotic cell envelops. Peptide membrane interactions arise from unique sequence motifs of the peptides that account for particular physicochemical properties. Membrane active peptides are mainly cationic, often primary or secondary amphipathic, and they interact with membranes depending on the composition of the bilayer lipids. Sequences of these peptides consist of short 5–30 amino acid sections derived from natural proteins or synthetic sources. Membrane active peptides can be designed using computational methods or can be identified in screenings of combinatorial libraries. This review focuses on strategies that were successfully applied to the design and optimization of membrane active peptides with respect to the fact that diverse features of successful peptide candidates are prerequisites for biomedical application. Not only membrane activity but also degradation stability in biological environments, propensity to induce resistances, and advantageous toxicological properties are crucial parameters that have to be considered in attempts to design useful membrane active peptides. Reliable assay systems to access the different biological characteristics of numerous membrane active peptides are essential tools for multi-objective peptide optimization.

Membrane-Active Peptides and Their Potential Biomedical Application

“…Also worth mentioning is the aspect highlighted by Kmeck et al, who sustained there is a limited possibility of using the MAPs in a unique therapeutic formulation. A viable solution could be the projection of a mutually reinforcing partnership between them and traditional and/or innovative pharmaceutical formulations [ 155 ] to overcome regular microbial resistance [ 20 ]. As a result, numerous peptide technologies, such as CPPs, peptide–drug conjugates, multifunctional peptides, and technologies emphasizing various administration methods, have been developing as promising alternatives to current therapies for emerging diseases like bacterial infections and tumor cells [ 156 ].…”

“…Biological instruments include viral vectors and physical ways of transfecting cells, from electroporation to microinjections. Detergents or membrane-active peptides are examples of chemical compounds that enable cellular entrance [ 20 ]. CPPs, also referred to as protein-transduction domains (PTDs), are a type of membrane-active peptides that consist of 5–30 amino acids and can transport a variety of biomolecules into cells, such as small drugs, small interfering RNA, proteins, peptide–nucleic acid (PNA), imaging agents, and vaccines [ 21 ].…”

Topoisomeric Membrane-Active Peptides: A Review of the Last Two Decades

“…that foster-or preventinteraction with membrane bilayers of diverse lipid compositions. These membrane-active peptides have been categorized into two main groups based on their mode of interaction: AMPs and anticancer peptides (ACP), both functioning as membrane disruptors, and CPPs, which translocate across the membrane to enter the cell [61]. Interestingly, these groups of peptides often exhibit similar properties, with instances where AMP/ACPs overlap with CPPs, and vice versa [62].…”