N-capping (N-cap) and C-capping (C-cap) in biologically active peptides, including specific amino acids or unconventional group motifs, have been shown to modulate activity against pharmacological targets by interfering with the peptide’s secondary structure, thus generating unusual scaffolds. The insertion of capping motifs in linear peptides has been shown to prevent peptide degradation by reducing its susceptibility to proteolytic cleavage, and the replacement of some functional groups by unusual groups in N- or C-capping regions in linear peptides has led to optimized peptide variants with improved secondary structure and enhanced activity. Furthermore, some essential amino acid residues that, when placed in antimicrobial peptide (AMP) capping regions, are capable of complexing metals such as Cu²⁺, Ni²⁺, and Zn²⁺, give rise to the family known as metallo-AMPs, which are capable of boosting antimicrobial efficacy, as well as other activities. Therefore, this review presents and discusses the different strategies for creating N- and C-cap motifs in AMPs, aiming at fine-tuning this class of antimicrobials.

Amphibians use their skin as an effective defense mechanism against predators and microorganisms. Specialized glands produce antimicrobial peptides (AMPs) that possess antioxidant properties, effectively reducing reactive oxygen species (ROS) levels. These peptides are promising candidates for treating diseases associated with oxidative stress (OS) and redox imbalance, including neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), as well as age-related conditions, like cardiovascular diseases and cancer. This review highlights the multifaceted roles of AMPs and antioxidant peptides (AOPs) in amphibians, emphasizing their protective capabilities against oxidative damage. They scavenge ROS, activate antioxidant enzyme systems, and inhibit cellular damage. AOPs often share structural characteristics with AMPs, suggesting a potential evolutionary connection and similar biosynthetic pathways. Peptides such as brevinin-1FL and Cath-KP demonstrate neuroprotective effects, indicating their therapeutic potential in managing oxidative stress-related diseases. The antioxidant properties of amphibian-derived peptides pave the way for novel therapeutic developments. However, a deeper understanding of the molecular mechanisms underlying these peptides and their interactions with oxidative stress is essential to addressing ROS-related diseases and advancing therapeutic strategies in clinical practice.

Eight new sulfide-based cyclic peptidomimetic analogues of solonamides A and B have been synthesized via solid-phase peptide synthesis and S_N2’ reaction on a Morita–Baylis–Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The analogues were prepared in moderate overall yields and did not show toxic effects on Staphylococcus aureus growth and were not toxic to human fibroblasts. Two of them inhibited the hemolytic activity of S. aureus, suggesting an interfering action in the bacterial quorum sensing similar to the one already reported for solonamides.

Latin America’s biodiversity accounts for approximately 60% of the world’s total, fueling scientific research into natural products, a highly relevant area in drug discovery to this day. This is accompanied by an increasing number of antimicrobial peptides (AMPs) derived from natural products in the region, which over the past decade have been redesigned through modifications, enhancements, and refinements of their physicochemical properties and antimicrobial potency, using approaches that range from rational design and structure–activity relationship (SAR) studies to artificial intelligence and machine learning methodologies. AMPs and their derivatives represent a vast chemical space with potential for antibacterial, antifungal, antiviral, and antiparasitic therapies, with emerging applications beyond infectious diseases. Over the years, studies have identified these peptides from a wide range of sources, including amphibians, reptiles, invertebrates, and microorganisms from South America, highlighting their diverse biological activities. This raises important questions about whether Latin America is a fertile source of inspiration for the development of AMPs. It also prompts an examination of the region’s historical and ongoing contributions to the field of natural and synthetic AMPs with anti-infective potential. Additionally, it highlights the need to assess the region’s progress in keeping pace with the recent advancements in engineering AMPs to combat resistant bacteria. This mini-review addresses these topics and related issues, exploring Latin America’s discoveries, challenges, and innovations in AMPs and their applications, particularly in anti-infective agents.

Amphibians use their skin as an efficient defense mechanism against predators and microorganisms. Within specialized glands, they produce antimicrobial peptides endowed with antioxidant properties that have demonstrated efficacy in reducing reactive oxygen species (ROS) levels. These peptides are considered promising candidates for treating diseases related to oxidative stress (OS). Neurodegenerative disorders (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), along with age-related conditions like cardiovascular diseases and cancer, have been connected to redox imbalance and the associated ROS. This review explores the characteristics of antioxidant peptides (AOP) identified in amphibians, elucidates their mechanisms of action against molecular targets involved in the diseases above, and provides insights into future prospects.