Glycodendriproteins: a synthetic glycoprotein mimic enzyme with branched sugar-display potently inhibits bacterial aggregation.
The continuing ability of bacteria to resist current antibiotic treatments highlights the need for alternative strategies for inhibiting their pathogenicity. Bacterial attachment is a major factor in infectivity and virulence. This key binding phase of bacteria to any potential host is mediated by adhesin proteins and so these present an attractive therapeutic target for antiinfective blocking strategies. However, the natural ligands to adhesins are large, typically complex molecules that are difficult to mimic with small molecules. We describe here a method that creates precise synthetic mimics of glycoproteins that are designed to bind adhesins. By using protein-degrading enzymes as the basis for these mimics we have created large-molecule protein ligands that inhibit aggregation of pathogenic bacteria at levels greater than a million-fold higher than small-molecule inhibitors of adhesins.
Rendle
Phillip M
PM
Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Seger
Andreas
A
Rodrigues
Joao
J
Oldham
Neil J
NJ
Bott
Richard R
RR
Jones
J Bryan
JB
Cowan
Marjorie M
MM
Davis
Benjamin G
BG
D000190:Actinomyces / Q000254:growth & development* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002241:Carbohydrates / Q000737:chemistry; D006023:Glycoproteins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011108:Polymers / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002241:Carbohydrates; D006023:Glycoproteins; D011108:Polymers