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 res...

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Bibliographic Details
Published in:Chemical biology & drug design 2007-03, Vol.69 (3), p.216-221
Main Authors: Falciani, Chiara, Lozzi, Luisa, Pini, Alessandro, Corti, Federico, Fabbrini, Monica, Bernini, Andrea, Lelli, Barbara, Niccolai, Neri, Bracci, Luisa
Format: Article
Language:English
Subjects:
Amino Acid Sequence
dendrimeric peptides
Endopeptidases - metabolism
Enkephalin, Leucine - chemistry
Enkephalin, Leucine - metabolism
half-life
Humans
Models, Molecular
Molecular Sequence Data
Neurotensin - analogs & derivatives
Neurotensin - chemistry
Neurotensin - metabolism
protease
Protein Binding
Protein Structure, Tertiary
stability
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Summary: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.
ISSN:1747-0277
1747-0285
DOI:10.1111/j.1747-0285.2007.00487.x