Antimicrobial peptide 1a

Purpose: Due to the emergence of multidrug resistance (MDR), traditional antileukemia drugs no longer meet the treatment needs. Therefore, new antileukemia drugs with different action mechanisms are urgently needed to cope with this situation. Materials and methods: Arminin 1a-C is an antimicrobial peptide (AMP) developed from the ancient metazoan marine Hydra. In this study, we first explored its antileukemia activity. Results: Our results showed that Arminin 1a-C formed an α-helical structure and efficaciously suppressed the viability of leukemia cell lines whether or not they were multidrug resistant or sensitive, and there were no obvious differences between these cell lines. Arminin 1a-C exhibited distinct selectivity between noncancerous and cancerous cell lines. Arminin 1a-C interfered with K562/adriamycin (ADM) cell (a kind of multidrug-resistant leukemia cell line) proliferation in a very rapid manner and formed pores in its cell membrane, making it difficult to develop resistance against Arminin 1a-C. Conclusion: Our data show that Arminin 1a-C possesses great potential as a therapeutic candidate for the treatment of multidrug-resistant leukemia.

Cupiennin 1a is an antimicrobial peptide found in the venom of the spider Cupiennius salei. A highly cationic peptide, its cell lysis activity has been found to vary between neutral and charged membranes. In this study, Hamiltonian replica-exchange molecular dynamics (HREMD) was used to determine the conformational ensemble of the peptide in both charged (pH 3) and neutral (pH 11) states. The obtained free energy landscapes demonstrated the conformational diversity of the neutral peptide. At high pH, the peptide was found to adopt helix-hinge-helix and disordered structures. At pH 3, the peptide is structured with a high propensity toward α-helices. The presence of these α-helices seems to assist the peptide in recognizing membrane surfaces. These results highlight the importance of the charged residues in the stabilization of the peptide structure and the subsequent effects of pH on the peptide's conformational diversity and membrane activity. These findings may provide insights into the antimicrobial activity of Cupiennin 1a and other amphipathic linear peptides toward different cell membranes.

Antimicrobial peptides (AMPs) represent an interesting class of molecules with expanding biological properties which make them a viable alternative for the development of future antibiotic drugs. However, for this purpose, some limitations must be overcome: (i) the poor biostability due to enzymatic degradation; (ii) the cytotoxicity at concentrations slightly higher than the therapeutic dosages; and (iii) the inefficient delivery to the target site at effective concentrations. Recently, a derivative of the frog skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, [Esc(1-21): GIFSKLAGKKIKNLLISGLKG-NH2] has been found to have a potent activity against the Gram-negative bacterium Pseudomonas aeruginosa; a slightly weaker activity against Gram-positive bacteria and interesting immunomodulatory properties. With the aim to optimize the antimicrobial features of Esc(1-21) and to circumvent the limitations described above, two different approaches were followed: (i) substitutions by non-coded amino acids, i.e., α-aminoisobutyric acid or d-amino acids; and (ii) peptide conjugation to gold nanoparticles. In this mini-review, we summarized the structural and functional properties of the resulting Esc(1-21)-derived compounds. Overall, our data may assist researchers in the rational design and optimization of AMPs for the development of future drugs to fight the worldwide problem of antibiotic resistance.