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Molecular Basis of Branched Peptides Resistance to Enzyme Proteolysis
Author(s) -
Falciani Chiara,
Lozzi Luisa,
Pini Alessandro,
Corti Federico,
Fabbrini Monica,
Bernini Andrea,
Lelli Barbara,
Niccolai Neri,
Bracci Luisa
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00487.x
Subject(s) - proteolysis , peptide , chemistry , biochemistry , molecular mass , dendrimer , monomer , proteolytic enzymes , peptide sequence , enzyme , organic chemistry , gene , polymer
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.