Exploration of novel cationic amino acid-enriched short peptides: design, SPPS, biological evaluation and in silico study.

Antimicrobial resistance (AMR) represents a critical challenge worldwide, necessitating the pursuit of novel approaches to counteract bacterial and fungal pathogens. In this context, we explored the potential of cationic amino acid-enriched short peptides, synthesized via solid-phase methods, as innovative antimicrobial candidates. Our comprehensive evaluation assessed the antibacterial and antifungal efficacy of these peptides against a panel of significant pathogens, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, and Aspergillus niger. Utilizing molecular docking techniques, we delved into the molecular interactions underpinning the peptides' action against these microorganisms. The results revealed a spectrum of inhibitory activities, with certain peptide sequences displaying pronounced effectiveness across various pathogens. These findings underscore the peptides' potential as promising antimicrobial agents, with molecular docking offering valuable insights into their mechanisms of action. This study enriches antimicrobial peptide (AMP) research by identifying promising candidates for further refinement and development toward therapeutic application, highlighting their significance in addressing the urgent issue of AMR.

A novel series of dipeptide derivatives containing indole-3-carboxylic acid conjugates as potential antimicrobial agents: the design, solid phase peptide synthesis, in vitro biological evaluation, and molecular docking study.

A new library of peptide-heterocycle hybrids consisting of an indole-3-carboxylic acid constituent conjugated with short dipeptide motifs was designed and synthesized by using the solid phase peptide synthesis methodology. All the synthesized compounds were characterized by spectroscopic techniques. Additionally, the synthesized compounds were subjected to in vitro antimicrobial activities. Two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and two Gram-positive (Streptococcus pyogenes and Staphylococcus aureus) were used for the evaluation of the antibacterial activity of the targeted dipeptide derivatives. Good antibacterial activity was observed for the screened analogues by comparing their activities with that of ciprofloxacin, the standard drug. Also, two fungi (Aspergillus niger and Candida albicans) were employed for the evaluation of the antifungal activity of the synthesized compounds. When compared to the standard drug Fluconazole, it was observed that the screened analogues exhibited good antifungal activity. In continuation, all the synthesized derivatives were subjected to integrated molecular docking studies and molecular dynamics simulations to investigate binding affinities, intermolecular interaction networks, and conformational flexibilities with deoxyribonucleic acid (DNA) gyrase and lanosterol-14-alpha demethylase. The molecular docking studies revealed that indole-3-carboxylic acid conjugates exhibited encouraging binding interaction networks and binding affinity with DNA gyrase and lanosterol-14 alpha demethylase to show antibacterial and antifungal activity, respectively. Such synthesis, biological activity, molecular dynamics simulations, and molecular docking studies of short peptides with an indole conjugate unlock the door for the near future advancement of novel medicines containing peptide-heterocycle hybrids with the ability to be effective as antimicrobial agents.

Synthesis and Evaluation of Biological Activities for a Novel 1,2,3,4-Tetrahydroisoquinoline Conjugate with Dipeptide Derivatives: Insights from Molecular Docking and Molecular Dynamics Simulations.

Peptide synthesis has opened new frontiers in the quest for bioactive molecules with limitless biological applications. This study presents the synthesis of a series of novel isoquinoline dipeptides using advanced spectroscopic techniques for characterization. These compounds were designed with the goal of discovering unexplored biological activities that could contribute to the development of novel pharmaceuticals. We evaluated the biological activities of novel compounds including their antimicrobial, antibacterial, and antifungal properties. The results show promising activity against Escherichia coli and potent antibacterial activity against MTCC 443 and MTCC 1688. Furthermore, these compounds demonstrate strong antifungal activity, outperforming existing standard drugs. Computational binding affinity studies of tetrahydroisoquinoline-conjugated dipeptides against E. coli DNA gyrase displayed significant binding interactions and binding affinity, which are reflected in antimicrobial activities of compounds. Our integrative significant molecular findings from both wet and dry laboratories would help pave a path for the development of antimicrobial therapeutics. The findings suggest that these isoquinoline-conjugated dipeptides could be excellent candidates for drug development, with potential applications in the fight against bacterial and fungal infections. This research represents an exciting step forward in the field of peptide synthesis and its potential to discover novel bioactive molecules with significant implications for human health.

A static and dynamic NMR study of 10-hydrazino-BODIPY.

10-Hydrazino-BODIPY, BoNHNH2 , presents slow rotation about the C10-NH bond that results in anisochronous 1 H and 13 C NMR signals. The assignment of the different signals has been made using traditional two-dimensional methods as well as spin-spin coupling constants and confirmed by DFT calculations (B3LYP) using the 6-311++G(d,p) basis set. The rotational barrier has been determined in three pairs of proton signals and compared with the calculated barrier.

Molecular Mechanism of Viscosity Sensitivity in BODIPY Rotors and Application to Motion-Based Fluorescent Sensors.

Viscosity in the intracellular microenvironment shows a significant difference in various organelles and is closely related to cellular processes. Such microviscosity in live cells is often mapped and quantified with fluorescent molecular rotors. To enable the rational design of viscosity-sensitive molecular rotors, it is critical to understand their working mechanisms. Herein, we systematically synthesized and investigated two sets of BODIPY-based molecular rotors to study the relationship between intramolecular motions and viscosity sensitivity. Through experimental and computational studies, two conformations (i.e., the planar and butterfly conformations) are found to commonly exist in BODIPY rotors. We demonstrate that the transformation energy barrier from the planar conformation to the butterfly conformation is strongly affected by the molecular structures of BODIPY rotors and plays a critical role in viscosity sensitivity. These findings enable rational structure modifications of BODIPY molecular rotors for highly effective protein detection and recognition.