A peptide sequence controls the physical properties of nanoparticles formed by peptide-polymer conjugates that respond to a protein kinase a signal.
We previously reported that poly(N-isopropylacrylamide) grafted with Peptide 1 (-GLRRASLG) and poly(ethylene glycol) changed its physical properties in response to an intracellular protein phosphorylation signal, protein kinase A (PKA) (Katayama, Y. et al. (2001) Macromolecules 34, 905). In this study, we investigated the effect of changing peptide structure on the lower critical solution temperature (LCST) of peptide-polymer conjugates, before and after phosphorylation with PKA. For Peptide 2 (Ac-LRRASL-), which has a formal net charge of +2 at physiological pH, the LCST of the conjugate decreased on phosphorylation. In contrast, the LCSTs of the conjugates with Peptide 3 (-ALRRASLE) and Peptide 4 (Ac-DWDALRRASL-), which have neutral net charges, were greatly increased. This suggests that the LCST of the polymer was mainly governed by two factors: the change in hydration around the polymer chain and the interpeptide electrostatic repulsion, resulting from phosphorylation. These polymers have potential for use as drug capsules that respond to cellular conditions.
Sonoda
Tatsuhiko
T
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
Nogami
Takashi
T
Oishi
Jun
J
Murata
Masaharu
M
Niidome
Takuro
T
Katayama
Yoshiki
Y
D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010766:Phosphorylation; D011108:Polymers / Q000737:chemistry*; D015398:Signal Transduction
D010455:Peptides; D011108:Polymers; D017868:Cyclic AMP-Dependent Protein Kinases