title: The action of fish peptide Orpotrin analogs on microcirculation.
abstract: In order to investigate the relationship between the primary structure of Orpotrin, a vasoactive peptide previously isolated from the freshwater stingray Potamotrygon gr. orbignyi, and its microcirculatory effects, three Orpotrin analogs were synthesized. The analogs have a truncated N-terminal with a His residue deletion and two substituted amino acid residues, where one Nle is substituted for one internal Lys residue and the third analog has a substitution of a Pro for an Ala (Orp-desH(1) , Orp-Nle and Orp-Pro/Ala, respectively). Only Orp-desH(1) could induce a lower vasoconstriction effect compared with the natural Orpotrin, indicating that besides the N-terminal, the positive charge of Lys and the Pro residues located at the center of the amino acid chain is crucial for this vasoconstriction effect. Importantly, the suggestions made with bioactive peptides were based on the molecular modeling and dynamics of peptides, the presence of key amino acids and shared activity in microcirculation, characterized by intravital microscopy. Moreover, this study has demonstrated that even subtle changes in the primary structure of Orpotrin alter the biological effects of this native peptide significantly, which could be of interest for biotechnological applications.
authors.affiliation: LETA (Laboratório Especial de Toxinologia Aplicada) Center for Applied Toxinology (CAT/CEPID), Butantan Institute, São Paulo, SP, Brazil.
authors.forename: Katia
authors.initials: K
authors.lastname: Conceição
authors.forename: Fernanda Miriane
authors.initials: FM
authors.lastname: Bruni
authors.forename: Juliane M
authors.initials: JM
authors.lastname: Santos
authors.forename: Robson Melo
authors.initials: RM
authors.lastname: Lopes
authors.forename: Elineide E
authors.initials: EE
authors.lastname: Marques
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Fernandez
authors.forename: Mônica
authors.initials: M
authors.lastname: Lopes-Ferreira
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005397:Fish Venoms / Q000737:chemistry* / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D008853:Microscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
chemical_list: D005397:Fish Venoms; C524673:Orpotrin; D010455:Peptides