title: Molecular basis of branched peptides resistance to enzyme proteolysis.
abstract: We found that synthetic peptides in the form of dendrimers become resistant to proteolysis. To determine the molecular basis of this resistance, different bioactive peptides were synthesized in monomeric, two-branched and tetra-branched form and incubated with human plasma and serum. Proteolytic resistance of branched multimeric sequences was compared to that of the same peptides synthesized as multimeric linear molecules. Unmodified peptides and cleaved sequences were detected by high pressure liquid chromatography and mass spectrometry. An increase in peptide copies did not increase peptide resistance in linear multimeric sequences, whereas multimericity progressively enhanced proteolytic stability of branched multimeric peptides. A structure-based hypothesis of branched peptide resistance to proteolysis by metallopeptidases is presented.
authors: Chiara
authors: C
authors: Falciani
authors: Luisa
authors: L
authors: Lozzi
authors: Alessandro
authors: A
authors: Pini
authors: Federico
authors: F
authors: Corti
authors: Monica
authors: M
authors: Fabbrini
authors: Andrea
authors: A
authors: Bernini
authors: Barbara
authors: B
authors: Lelli
authors: Neri
authors: N
authors: Niccolai
authors: Luisa
authors: L
authors: Bracci
mesh_terms: D000595:Amino Acid Sequence; D010450:Endopeptidases / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D009496:Neurotensin; D004743:Enkephalin, Leucine; D010450:Endopeptidases