Cell-penetrating peptides (CPP) are a family of peptides able to penetrate the cell membrane. This group of compounds has attracted consideration as potential therapeutic tools for the delivery of various substances into cells. Here, we investigated possible interactions between several CPP synthesized in our laboratory and the vascular action of phenylephrine. We used isolated rat tail artery and examined the influence of pretreatment by seven different CPP on the concentration-response curve induced by the α1 receptor agonist phenylephrine. Peptides were synthesized by solid-phase peptide synthesis (SPPS) using the 9-fluorenylmethoxycarbonyl (Fmoc) method. Among the seven different polypeptides, i.e., TP10 (transportan-10), [Lys(AAc)13]TP, [Lys(CAc)13]TP, [Lys(GAc)13]TP, [Lys(TAc)13]TP, [Lys(UAc)13]TP and [Lys(Ac)13]TP, only TP10 and [Lys(AAc)13]TP, both at a concentration of 1 μM (the lowest concentration inducing a significant change in the contraction of isolated rat stomach in our pilot study), rendered rat tail artery more sensitive to phenylephrine; the relative potency increased significantly. Conversely, [Lys(Ac)13]TP strongly decreased the efficacy of phenylephrine.

Mastoparan (MP) is an antimicrobial cationic tetradecapeptide with the primary structure INLKALAALAKKIL-NH2. This amphiphilic α-helical peptide was originally isolated from the venom of the wasp Paravespula lewisii. MP shows a variety of biological activities, such as inhibition of the growth of Gram-positive and Gram-negative bacteria, as well as hemolytic activity and activation of mast cell degranulation. Although MP appears to be toxic, studies have shown that its analogs have a potential therapeutic application as antimicrobial, antiviral and antitumor agents. In the present study we have designed and synthesized several new chimeric mastoparan analogs composed of MP and other biologically active peptides such as galanin, RNA III inhibiting peptide (RIP) or carrying benzimidazole derivatives attached to the ε-amino side group of Lys residue. Next, we compared their antimicrobial activity against three reference bacterial strains and conformational changes induced by membrane-mimic environments using circular dichroism (CD) spectroscopy. A comparative analysis of the relationship between the activity of peptides and the structure, as well as the calculated physicochemical parameters was also carried out. As a result of our structure–activity study, we have found two analogs of MP, MP-RIP and RIP-MP, with interesting properties. These two analogs exhibited a relatively high antibacterial activity against S. aureus compared to the other MP analogs, making them a potentially attractive target for further studies. Moreover, a comparative analysis of the relationship between peptide activity and structure, as well as the calculated physicochemical parameters, may provide information that may be useful in the design of new MP analogs.