Replacement of a proline with silaproline causes a 20-fold increase in the cellular uptake of a Pro-rich peptide.
The results presented here show that elementary design enhancements have led to a 20-fold increase in the cellular uptake properties of a Pro-rich cell-penetrating peptide. These results are relevant not only due to the increasing interest in using CPPs as molecular shuttles for intracellular drug delivery but also because they illustrate the power of combining conformational analysis with rational design to modulate the behavior of biologically active compounds.
Pujals
Sílvia
S
Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Josep Samitier 1, E-08028 Barcelona, Spain.
Fernandez-Carneado
Jimena
J
Kogan
Marcelo J
MJ
Martinez
Jean
J
Cavelier
Florine
F
Giralt
Ernest
E
D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism / Q000379:methods; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D006367:HeLa Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008968:Molecular Conformation; D017646:Organosilicon Compounds / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D055232:Proline-Rich Protein Domains; D021381:Protein Transport / Q000187:drug effects; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D004337:Drug Carriers; D017646:Organosilicon Compounds; D010455:Peptides; C455420:silaproline; D011392:Proline