ABSTRACT
Antimicrobial peptides are widely distributed in nature; they play important roles in several aspects of innate immunity and may provide a basis for the design of novel therapeutic agents. In this study, C-amidated tritrpticin, a 13 amino acid tryptophan-rich antimicrobial peptide derived from a porcine cathelicidin, was tested against Trichomonas vaginalis, a protozoan that causes a serious non-viral sexually transmitted disease associated with preterm birth, low birth weight, and high risk of HIV-1 infection. Tritrpticin was selected due to its reasonably easy synthesis and because analogs with lower toxicity may be designed. Our results show that tritrpticin-NH(2) at either 100 or 200 µg/ml (52.5 or 105 µM) clearly reduces the viability and growth of Trichomonas vaginalis. Together with tritrpticin-NH(2), sodium bicarbonate further limited trichomonad growth. Additionally, a low concentration of metronidazole (5.8 µM), the most commonly used medication for Trichomonas vaginalis, was more effective against the growth of the parasite when it was combined with tritrpticin-NH(2).
Subject(s)
Antimicrobial Cationic Peptides/pharmacology , Antiprotozoal Agents/pharmacology , Oligopeptides/pharmacology , Trichomonas vaginalis/drug effects , Drug Synergism , Female , Humans , Metronidazole/pharmacology , Microbial Viability/drug effects , Parasitic Sensitivity Tests , Sodium Bicarbonate/pharmacology , Trichomonas vaginalis/growth & development , Trichomonas vaginalis/physiologyABSTRACT
Two synthetic procedures for HYNIC oxytocin labeling were developed: one based on an orthogonal protection approach and the other with prelabeled (Boc)HYNIC-(Fmoc) amino acids. Both procedures were compared and applied to the preparation of several HYNIC-oxytocin derivatives where ligand position and amino acid (lysine and phenylalanine) were varied. Additionally, an oxytocin derivative labeled with HYNIC in the alpha-amino group of the Cys1 residue was also prepared. 99mTc-ethylendiaminediacetic acid (EDDA) labeling efficiencies were examined for all the derivatives, resulting in two candidates which showed affinity for the oxytocin receptor. Further biochemical experiments demonstrated that 99mTc-EDDA/HYNIC-Cys1-OT-CONH2 could be used as a potential radiopharmaceutical for breast cancer diagnosis.
