De novo design of biomimetic antimicrobial polymers.
The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor with both fundamental and practical implications. Recently, a number of nonnatural peptides with designed sequences have been elaborated to provide biologically active structures; in particular, facially amphiphilic peptides built from beta-amino acids have been shown to mimic both the structures as well as the biological function of natural antimicrobial peptides such as magainins and cecropins. However, these natural peptides as well as their beta-peptide analogues are expensive to prepare and difficult to produce on a large scale, limiting their potential use to certain pharmaceutical applications. We therefore have designed a series of facially amphiphilic arylamide polymers that capture the physical and biological properties of this class of antimicrobial peptides, but are easy to prepare from inexpensive monomers. The design process was aided by molecular calculations with density functional theory-computed torsional potentials. This new class of amphiphilic polymers may be applied in situations where inexpensive antimicrobial agents are required.
Tew
Gregory N
GN
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA.
Liu
Dahui
D
Chen
Bin
B
Doerksen
Robert J
RJ
Kaplan
Justin
J
Carroll
Patrick J
PJ
Klein
Michael L
ML
DeGrado
William F
WF
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D009757:Nylons / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D012984:Software; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D009757:Nylons; D010455:Peptides