Molecular basis of branched peptides resistance to enzyme proteolysis.
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.
Falciani
Chiara
C
Lozzi
Luisa
L
Pini
Alessandro
A
Corti
Federico
F
Fabbrini
Monica
M
Bernini
Andrea
A
Lelli
Barbara
B
Niccolai
Neri
N
Bracci
Luisa
L
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
D009496:Neurotensin; D004743:Enkephalin, Leucine; D010450:Endopeptidases