Abstract

POLYAMINE-BASED PEPTIDOMIMETICS AS PROMISING ANTIMICROBIAL AGENTS: STRUCTURE ACTIVITY RELATIONSHIPS AND PHARMACEUTICAL APPLICATIONS

Syra A. S.*, Vani V., Dr. Sreeja S., Shifa Sahad, Amina Salim

ABSTRACT

Molecules that contain polyamines and carry the definite positive charge typical of natural polyamines and peptides are referred to as polyamine-containing peptidomimetics. The protonation of amine groups makes it possible to interact with anion sites, such as bacterial membranes. The diverse use of amino acid residues, hydrophobic fragments, and suitable linkers enables the modification of charge, solubility, conformation, membrane permeability, and biological activity of polyamine-containing peptidomimetics. The range of biological activity encompasses antimicrobial, antibiofilm, anticancer, antiviral, and other effects, which are highly significant for research. The use of polyamine-based peptidomimetics in drug discovery is supported by the optimal balance of charge and hydrophobicity needed for effective interaction with bacterial membranes without harming mammalian cells. Structure-activity relationship analysis showed that the chemical properties, size, and charge of the polyamine component, as well as the nature of amino acid residues, hydrophobic fragments, and linkers, influence the activity of polyamine-containing peptidomimetics. This review offers an overview of the structure-biological activity relationships, mechanisms of action, and pharmaceutical use of polyamine-based peptidomimetics as antimicrobial agents.

Keywords: Polyamines; Peptidomimetics; Amino acids; Antimicrobial peptides; Antibacterial activity; Antibiofilm; Structure–activity relationship.