Int. J. Mol. Sci. 2015, 16, 23867-23880; doi:10.3390/ijms161023867 International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates Ashish Punia 1,2 , Kevin Lee 3 , Edward He 3 , Sumit Mukherjee 4,† , Andrew Mancuso 4,† , Probal Banerjee 5 and Nan-Loh Yang 1,2, * 1 Department of Chemistry and Center for Engineered Polymeric Materials, College of Staten Island, Staten Island, New York, NY 10016, USA; E-Mail: apunia@gradcenter.cuny.edu 2 Ph. D. Program in Chemistry at the Graduate Center of the City University of New York, New York, NY 10016, USA 3 Department of Chemistry, Macaulay Honors College, New York, NY 10016, USA; E-Mails: kevin.lee@macaulay.cuny.edu (K.L.); edward.he@macaulay.cuny.edu (E.H.) 4 Ph.D. Program in Biochemistry at the Graduate Center of the City University of New York, New York, NY 10016, USA; E-Mails: smukherjee@gradcenter.cuny.edu (S.M.); amancuso@gradcenter.cuny.edu (A.M.) 5 Department of Chemistry and Center for Developmental Neuroscience, College of Staten Island, Staten Island, New York, NY 10016, USA; E-Mail: probal.banerjee@csi.cuny.edu † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: nanloh.yang-cepm@csi.cuny.edu; Tel.: +1-718-982-3926; Fax: +1-718-982-3899. Academic Editors: Antonella Piozzi and Iolanda Francolini Received: 6 September 2015 / Accepted: 29 September 2015 / Published: 9 October 2015 Abstract: Synthetic amphiphilic polymers have been established as potentially efficient agents to combat widespread deadly infections involving antibiotic resistant superbugs. Incorporation of poly(ethylene glycol) (PEG) side chains into amphiphilic copolymers can reduce their hemolytic activity while maintaining high antibacterial activity. Our study found that the incorporation of PEG has substantially different effects on the hemolytic and antibacterial activities of copolymers depending on structural variations in the positions of cationic centers relative to hydrophobic groups. The PEG side chains dramatically reduced the hemolytic activities in copolymers with hydrophobic hexyl and cationic groups on the OPEN ACCESS