PMID- 14733596
OWN - NLM
STAT- MEDLINE
DCOM- 20040309
LR  - 20141120
IS  - 1043-1802 (Print)
IS  - 1043-1802 (Linking)
VI  - 15
IP  - 1
DP  - 2004 Jan-Feb
TI  - Dendritic polyglycerol sulfates as new heparin analogues and potent inhibitors of 
      the complement system.
PG  - 162-7
AB  - Due to several limitations of heparin, a widely used antithrombotic drug, there 
      is large interest to develop alternatives. The aim of the presented study was to 
      produce fully synthetic highly branched heparin mimetics. For this purpose, a new 
      type of 'treelike' polysulfated polymers based on dendritic polyglycerol was 
      synthesized. An efficient synthetic approach has been chosen to prepare several 
      polyglycerol sulfates with different molecular weights as well as a polyglycerol 
      carboxylate analogue and to evaluate them for their anticoagulant and 
      anticomplementary activities. In contrast to the nonderivatized and the 
      carboxylated polyglycerols, the polyglycerol sulfates prolong the activated 
      partial thromboplastin time (APTT) and thrombin time (TT) and inhibit both the 
      classical (CCA) and alternative complement activation (ACA). Whereas their 
      anticoagulant activity in the APTT and in the TT amounts to 5.7-8.1% and 
      15.7-33.6%, respectively, of that of unfractionated heparin (UFH), their CCA and 
      ACA inhibitory activity is 13.4-23.9 and 2.7-3.7 times, respectively, higher. In 
      contrast to sulfated polysaccharides, the activities are not clearly dependent on 
      the molecular weight, which might be due to the globular 3D-structure of the 
      dendritic molecules. Due to the coherence between coagulation, complement 
      activation and inflammation in the pathophysiology of numerous diseases, 
      polyglycerol sulfates with both anticoagulant and anticomplementary activities 
      represent promising candidates for the development of potential drugs.
FAU - Turk, Holger
AU  - Turk H
AD  - Freiburg Materials Research Center, Albert-Ludwigs-University of Freiburg, 
      Stefan-Meier-Strasse 21, 79104 Freiburg, Germany.
FAU - Haag, Rainer
AU  - Haag R
FAU - Alban, Susanne
AU  - Alban S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Anticoagulants)
RN  - 0 (Complement Inactivator Proteins)
RN  - 0 (Polymers)
RN  - 25618-55-7 (polyglycerol)
RN  - 9005-49-6 (Heparin)
RN  - PDC6A3C0OX (Glycerol)
SB  - IM
MH  - Adult
MH  - Algorithms
MH  - Anticoagulants/*chemical synthesis/*pharmacology
MH  - Complement Inactivator Proteins/*chemical synthesis/*pharmacology
MH  - Complement Pathway, Alternative/drug effects
MH  - Complement Pathway, Classical/drug effects
MH  - Glycerol/*chemistry/*pharmacology
MH  - Heparin/analogs & derivatives/*chemical synthesis/*pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Magnetic Resonance Spectroscopy
MH  - Molecular Weight
MH  - Polymers/*chemistry/*pharmacology
MH  - Structure-Activity Relationship
EDAT- 2004/01/22 05:00
MHDA- 2004/03/10 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/03/10 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
AID - 10.1021/bc034044j [doi]
PST - ppublish
SO  - Bioconjug Chem. 2004 Jan-Feb;15(1):162-7. doi: 10.1021/bc034044j.