Enzyme-Activatable Cell-Penetrating Peptides through a Minimal Side Chain Modification.
Activatable cell-penetrating peptides are of great interest in drug delivery because of their enhanced selectivity which can be controlled by the external stimuli that trigger their activation. The use of a specific enzymatic reaction to trigger uptake of an inert peptide offers a relevant targeting strategy because the activation process takes place in a short time and only in areas where the specific cell surface enzyme is present. To this aim, the lysine side chain of Tat peptides was modified with an enzyme-cleavable domain of minimal size. This yielded blocked Tat-peptides which were inactive but that could be activated by coincubation with the selected enzymes.
Radboud University Nijmegen, Institute for Molecules and Materials, Bio-organic Chemistry, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Saskia A
SA
Bode
Radboud University Nijmegen, Institute for Molecules and Materials, Bio-organic Chemistry, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Morten B
MB
Hansen
Radboud University Nijmegen, Institute for Molecules and Materials, Bio-organic Chemistry, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Roy A J F
RA
Oerlemans
Radboud University Nijmegen, Institute for Molecules and Materials, Bio-organic Chemistry, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Jan C M
JC
van Hest
Radboud University Nijmegen, Institute for Molecules and Materials, Bio-organic Chemistry, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Dennis W P M
DW
Löwik
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry
D057846:Cell-Penetrating Peptides; D015696:Gene Products, tat; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D008239:Lysine