Chapter

Host Defense Peptides and Their Potential as Therapeutic Agents

pp 253-290

Date:

How to Teach Old Antibiotics New Tricks

  • Stephanie DeshayesAffiliated withDepartment of Bioengineering, University of California
  • , Michelle W. LeeAffiliated withDepartment of Bioengineering, University of CaliforniaDepartment of Chemistry & Biochemistry, University of California
  • , Nathan W. SchmidtAffiliated withDepartment of Pharmaceutical Chemistry, University of California
  • , Wujing XianAffiliated withDepartment of Bioengineering, University of CaliforniaDepartment of Chemistry & Biochemistry, University of California
  • , Andrea KaskoAffiliated withDepartment of Bioengineering, University of CaliforniaCalifornia Nano Systems Institute, University of California
  • , Gerard C. L. WongAffiliated withDepartment of Bioengineering, University of CaliforniaDepartment of Chemistry & Biochemistry, University of CaliforniaCalifornia Nano Systems Institute, University of California Email author 

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Abstract

Antimicrobial peptides (AMPs), or more generally host defense peptides, have broad-spectrum antimicrobial activity and use nonspecific interactions to target generic features common to the membranes of many pathogens. As a result, development of resistance to such natural defenses is inhibited compared to conventional antibiotics. The disadvantage of AMPs, however, is that they are often not very potent. In contrast, traditional antibiotics typically have strong potency, but due to a broad range of bacterial defense mechanisms, there are many examples of resistance. Here, we explore the possibility of combining these two classes of molecules. In the first half of this chapter, we review the fundamentals of membrane curvature generation and the various strategies recently used to mimic this membrane activity of AMPs using different classes of synthetic molecules. In the second half, we show that it is possible to impart membrane activity to molecules with no previous membrane activity, and summarize some of our recent works which aim to combine advantages of traditional antibiotics and AMPs into a single molecule with multiple mechanisms of killing as well as multiple mechanisms of specificity.