Novel cyclopeptides for the design of MMP directed delivery devices: a novel smart delivery paradigm.
OBJECTIVE
Matrix metalloproteinases (MMP) are a family of proteolytic enzymes, the expression of which in a key step of tumor progression has been better defined recently. The studies highlighted the ongoing need for very specific inhibitors, substrates or release devices designed to be selective for one or at least very few MMPs.


METHODS
This report deals with the design, synthesis and in vitro evaluation of linear and especially novel cyclic peptidic moieties, embodying MMP cleavable sequences designed to answer these questions. FRET (fluorescence resonance energy transfer) labelling via chromophore-modified amino-acids was used to give access to enzyme kinetics.


RESULTS
Evaluation of these peptides showed that cyclisation gives rise to high specificity for certain MMP, suggesting that this approach could provide very specific MMP substrate. Moreover, cyclic structures present a very good plasma stability.


CONCLUSIONS
These original derivatives could allow the design of MMP-controlled delivery devices, the specificity of which will be retained in complex biological media and in vivo.
Moustoifa
El-Farouck
el-F
Université Victor Segalen Bordeaux 2, CNRS UMR 5084 Bio-Organic Chemistry Group, 146 rue Léo Saignat, F-33076, Bordeaux Cedex, France.
Alouini
Mohamed-Anis
MA
Salaün
Arnaud
A
Berthelot
Thomas
T
Bartegi
Aghleb
A
Albenque-Rubio
Sandra
S
Déléris
Gérard
G
D000595:Amino Acid Sequence; D003500:Cyclization; D016503:Drug Delivery Systems; D015195:Drug Design; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007700:Kinetics; D061965:Matrix Metalloproteinase Inhibitors; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000627:therapeutic use*
D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides
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