Conformational and functional effects induced by D- and L-amino acid epimerization on a single gene encoded peptide from the skin secretion of Hypsiboas punctatus

Skin secretion of Hypsiboas punctatus is the source of a complex mixture of bioactive compounds where peptides and small proteins prevail, similarly to many other amphibians. Among dozens of molecules isolated from H. punctatus in a proteomic based approach, we report here the structural and functio...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e59255-e59255
Main Authors: de Magalhães, Mariana T Q, Barbosa, Eder A, Prates, Maura V, Verly, Rodrigo M, Munhoz, Victor Hugo O, de Araújo, Ivan E, Bloch, Jr, Carlos
Format: Article
Language:English
Subjects:
Acids
Amino Acid Motifs
Amino Acid Sequence
Amino acids
Amino Acids - chemistry
Amphibia
Amphibians
Analysis
Animals
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - genetics
Antimicrobial Cationic Peptides - pharmacology
Antimicrobial Cationic Peptides - secretion
Anura - genetics
Base Sequence
Bioactive compounds
Biology
Edman degradation
Genetic aspects
Hyla
Ion mobility
Ionic mobility
Laboratories
Male
Mass Spectrometry
Mass spectroscopy
Metabolism
Mice
Mice, Knockout
Microbial Sensitivity Tests
Models, Molecular
Molecular Sequence Data
Narcotics
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular
Peptide synthesis
Peptides
Peptides - chemistry
Peptides - genetics
Peptides - pharmacology
Peptides - secretion
Protein Conformation
Proteins
Reptiles & amphibians
Secretion
Sequence Alignment
Skin
Skin - metabolism
Stroke
Structure-function relationships
Taste
Taste Perception - genetics
TRPM Cation Channels - deficiency
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Summary:Skin secretion of Hypsiboas punctatus is the source of a complex mixture of bioactive compounds where peptides and small proteins prevail, similarly to many other amphibians. Among dozens of molecules isolated from H. punctatus in a proteomic based approach, we report here the structural and functional studies of a novel peptide named Phenylseptin (FFFDTLKNLAGKVIGALT-NH2) that was purified as two naturally occurring D- and L-Phes configurations. The amino acid epimerization and C-terminal amidation for both molecules were confirmed by a combination of techniques including reverse-phase UFLC, ion mobility mass spectrometry, high resolution MS/MS experiments, Edman degradation, cDNA sequencing and solid-phase peptide synthesis. RMSD analysis of the twenty lowest-energy (1)H NMR structures of each peptide revealed a major 90° difference between the two backbones at the first four N-terminal residues and substantial orientation changes of their respective side chains. These structural divergences were considered to be the primary cause of the in vitro quantitative differences in antimicrobial activities between the two molecules. Finally, both molecules elicited equally aversive reactions in mice when delivered orally, an effect that depended entirely on peripheral gustatory pathways.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0059255