Enhancing Membrane-Disruptive Activity via Hydrophobic Phenylalanine and Lysine Tethered to Poly(aspartic acid).

08:00 EDT 1st April 2019 | BioPortfolio

Summary of "Enhancing Membrane-Disruptive Activity via Hydrophobic Phenylalanine and Lysine Tethered to Poly(aspartic acid)."

Amphiphilic polymers with pH-responsive abilities have been widely used as carriers for intracellular delivery of bioactive substances, while their membrane-disruptive activity exerted on cells is a critical characteristic that determines the delivery efficiency. Herein, we present a novel method to prepare amphiphilic and pH-responsive polymers by chemically tethering L-phenylalanine methyl ester and followed by Nε-carbobenzyloxy-L-lysine benzyl ester to the side carboxylic acid groups of poly(aspartic acid). The obtained phenylalanine- and lysine-grafted polymer (PAsp-g-Phe)-g-Lys demonstrated enhanced membrane-disruptive activity at pH 7.4 in comparison with PAsp-g-Phe. Moreover, the pH-responsive behavior of the grafted polymers caused by the significantly intensified hydrophobicity could be modulated by the tethered amount of hydrophobic amino acids with phenyl groups. The prepared amphiphilic (PAsp-g-Phe)-g-Lys could facilitate entry of calcein into NIH/3T3 and HeLa cells at the physiological pH values, possibly due to locally chemical destabilization of cell membranes by the interaction between the polymer and membrane bilayers. Therefore, we have provided a feasible approach to prepare pH-responsive polymers with enhanced membrane-disruptive activity, and the phenylalanine and lysine-grafted polymers could be a potential candidate for intracellular delivery of bioactive molecules in biomedical applications.


Journal Details

This article was published in the following journal.

Name: ACS applied materials & interfaces
ISSN: 1944-8252


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Medical and Biotech [MESH] Definitions

An enzyme that activates phenylalanine with its specific transfer RNA. EC

A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).

A metallocarboxypeptidase that removes C-terminal lysine and arginine from biologically active peptides and proteins thereby regulating their activity. It is a zinc enzyme with no preference shown for lysine over arginine. Pro-carboxypeptidase U in human plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U.

A histone-lysine N-methyltransferase and catalytic subunit of Polycomb Repressive Complex 2. It methylates LYSINE 9 (H3K9me) and LYSINE 27 (H3K27me) of HISTONE H3, leading to transcriptional repression of the affected target gene. EZH2 also methylates non-histone proteins such as GATA4 TRANSCRIPTION FACTOR and the nuclear receptor RORA. It regulates CIRCADIAN CLOCKS via histone methylation at the PROMOTER REGIONS of the circadian genes and its repressive activity is also important for the identity and differentiation of EMBRYONIC STEM CELLS.

An enzyme that catalyzes the deamination of PHENYLALANINE to form trans-cinnamate and ammonia.

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