Peptide Design Principles for Antimicrobial Applications

Marcelo D T Torres; Shanmugapriya Sothiselvam; Timothy K Lu; Cesar de la Fuente-Nunez

doi:10.1016/j.jmb.2018.12.015

Peptide Design Principles for Antimicrobial Applications

J Mol Biol. 2019 Aug 23;431(18):3547-3567. doi: 10.1016/j.jmb.2018.12.015. Epub 2019 Jan 3.

Authors

Marcelo D T Torres¹, Shanmugapriya Sothiselvam², Timothy K Lu², Cesar de la Fuente-Nunez³

Affiliations

¹ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA 02139, USA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 09210580, Brazil.
² Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA 02139, USA.
³ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA 02139, USA. Electronic address: cfuente@mit.edu.

PMID: 30611750
DOI: 10.1016/j.jmb.2018.12.015

Abstract

The increased incidence of bacterial resistance to available antibiotics represents a major global health problem and highlights the need for novel anti-infective therapies. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. AMPs are versatile, have almost unlimited sequence space, and can be tuned for broad-spectrum or specific activity against microorganisms. However, several obstacles remain to be overcome in order to develop AMPs for medical use, such as toxicity, stability, and bacterial resistance. We lack standard experimental procedures for quantifying AMP activity and do not yet have a clear picture of the mechanisms of action of AMPs. The rational design of AMPs can help solve these issues and enable their use as new antimicrobials. Here we provide an overview of the main physicochemical features that can be engineered to achieve enhanced bioactivity and describe current strategies being used to design AMPs.

Keywords: antibiotic resistance; antimicrobial peptides; design principles; peptide design; physicochemical features.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Infective Agents / chemistry*
Anti-Infective Agents / pharmacology
Antimicrobial Cationic Peptides / chemistry*
Antimicrobial Cationic Peptides / genetics
Antimicrobial Cationic Peptides / pharmacology
Chemical Phenomena
Computational Chemistry
Hydrophobic and Hydrophilic Interactions
Mutagenesis, Site-Directed
Peptides / chemistry*
Peptides / genetics
Peptides / pharmacology

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Antimicrobial Cationic Peptides
Peptides