Structural Analysis and Activity Correlation of Amphiphilic Cyclic Antimicrobial Peptides Derived from the [W\u3csub\u3e4\u3c/sub\u3eR\u3csub\u3e4\u3c/sub\u3e] Scaffold

In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W4R4], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure–activity relationships (SARs) of a series of cyclic peptides derived from the [W4R4] scaffold, including the first synthesis and evaluation of [W4R4(DKP)]. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results revealed distinct SARs linking antimicrobial activity to parameters such as conformational plasticity, immersion depth in the bilayer, and population of the membrane binding mode. Notably, [W4R5] exhibited an optimal “activity/binding to the bacterial membrane” pattern. This multidisciplinary approach efficiently decoded finely regulated SAR profiles, laying a foundation for the rational design of novel antimicrobial peptides

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures

Production and Utilization of Keratin and Sericin-Based Electro-Spun Nanofibers: A Comprehensive Review

This article review is devoted to throw the light on the unique characteristics of keratin- and sericin-based electro-spun nanofibers which make them suitable for various applications in different fields. The principles of electro-spinning together with the various devices usually used to fabricate nanofibers are also highlighted. The chemistry of keratin and sericin bio-polymers and the methods of extraction from their respective natural resources, such as wool and natural silk fibers, were criticized. Blending of keratin or sericin with various natural and synthetic polymeric materials to improve their rheological properties to obtain electro-spinnable composite suitable for production of functional nano-fibrous mat was discussed. Incorporation of nanosized metals and metal oxides as well as bioactive materials into keratin and sericin-based electro-spun nanofibers imparts new functions to the produced nanofibres. The utilization of these functional nano-fibrous mats in biomedical, filtration and smart textile applications was illustrated. The current status and future prospects of the electro-spun nanofibers were highlighted