Skip to main content

De novo Designed Lipopolysaccharide Binding Peptides: Structure Based Development of Antiendotoxic and Antimicrobial Drugs

Buy Article:

$63.00 plus tax (Refund Policy)

Abstract:

Lipopolysaccharide (LPS), the glycolipid of the outer membrane of Gram-negative bacteria, is critically involved in health and diseases. LPS facilitates the survival of pathogens by imposing a permeability barrier against antibiotics and antimicrobial peptides. LPS, also termed as endotoxin, functions as a potent inducer of innate immunity. Interception of endotoxin in systemic circulation by immune cells e.g. macrophages is essential to mount surveillance against invading microbes. However, a hyper-activated immune response may lead to the overwhelming production of tissue damaging cytokines TNF-α, IL-1, IL-6 and free radicals that may cause multiple organ failures or septic shock syndromes. The sepsis or septic shock is the major cause of mortality; 120,000 deaths/year occur in the United States alone, in the intensive care units. To-date, no therapeutic is available to combat sepsis mediated lethality. Furthermore, bacterial resistance against commonly used antibiotics has been increasing at an alarming rate necessitating a search for antibacterial agents with novel mode of actions. LPS could be a valid drug target for the development of antiendotoxic and antimicrobial compounds. In this article, recent advances in structural basis of LPS recognition by its receptor proteins and mode of actions of antimicrobial peptides defensins and cathelicidins are reviewed. Our research has identified, through de novo design, antimicrobial and endotoxin interacting β-boomerang peptides. Structure-activity correlations (SAR) of these peptides have been discussed, highlighting future design to achieve potent LPS neutralizing molecules.

Keywords: Lipopolysaccharide; NMR; STD-NMR; antimicrobial peptide; de novo designed peptide; endotoxin; sepsis; tr-NOE

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710791959756

Affiliations: School of Biological Sciences, Nanyang Technological University, Singapore.

Publication date: September 1, 2010

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
ben/cmc/2010/00000017/00000027/art00008
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more