PMID- 11562342
OWN - NLM
STAT- MEDLINE
DCOM- 20020325
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 103
IP  - 4
DP  - 2001 Aug 15
TI  - Characterisation of the anticoagulant properties of a range of structurally 
      diverse sulfated oligosaccharides.
PG  - 325-35
AB  - In this study, 17 sulfated oligosaccharides were assessed by the activated 
      partial thromboplastin time (APTT) test for their anticoagulant activity and nine 
      were found to exhibit significant activity. Chain length, monosaccharide makeup, 
      and linkage all appear to be critical factors in determining anticoagulant 
      activity, with the most active compounds being five- to sixfold less potent than 
      unfractionated heparin (UFH). Phosphomannopentaose sulfate (PI-88), one of the 
      most active sulfated oligosaccharides and a promising anticancer drug, was 
      selected for further study. PI-88 gave a more linear APTT dose-response curve and 
      displayed less patient-to-patient variation than UFH, with its activity being 
      neutralised by protamine sulfate. However, PI-88 showed considerable 
      species-to-species variation in its anticoagulant effect. It was found that PI-88 
      acted as an anticoagulant by enhancing the ability of heparin cofactor II (HCII) 
      to inhibit thrombin, and did not act via antithrombin III (AT-III) in either 
      inhibiting Factor Xa or thrombin. PI-88 also mildly prolonged the prothrombin 
      time (PT), whilst it had no platelet pro-aggregatory activity, nor did it 
      demonstrate direct fibrinolytic activity. Thus, PI-88 represents a potential 
      antithrombotic agent deserving further study.
FAU - Wall, D
AU  - Wall D
AD  - Research and Development Unit, Australian Red Cross Blood Service-Victoria, 
      Melbourne, VIC, Australia.
FAU - Douglas, S
AU  - Douglas S
FAU - Ferro, V
AU  - Ferro V
FAU - Cowden, W
AU  - Cowden W
FAU - Parish, C
AU  - Parish C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Anticoagulants)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Oligosaccharides)
RN  - 0 (Sulfuric Acid Esters)
RN  - 0 (phosphomannopentaose sulfate)
RN  - 81604-65-1 (Heparin Cofactor II)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/chemistry/metabolism/*pharmacology
MH  - Antineoplastic Agents/metabolism/pharmacology
MH  - Antithrombin III/pharmacology
MH  - Blood Coagulation/*drug effects
MH  - Drug Synergism
MH  - Heparin/metabolism/pharmacology
MH  - Heparin Cofactor II/pharmacology
MH  - Humans
MH  - Oligosaccharides/chemistry/metabolism/*pharmacology
MH  - Partial Thromboplastin Time
MH  - Species Specificity
MH  - Structure-Activity Relationship
MH  - Sulfuric Acid Esters/chemistry/metabolism/pharmacology
MH  - Thrombin/antagonists & inhibitors
EDAT- 2001/09/20 10:00
MHDA- 2002/03/26 10:01
CRDT- 2001/09/20 10:00
PHST- 2001/09/20 10:00 [pubmed]
PHST- 2002/03/26 10:01 [medline]
PHST- 2001/09/20 10:00 [entrez]
AID - S0049-3848(01)00314-0 [pii]
AID - 10.1016/s0049-3848(01)00314-0 [doi]
PST - ppublish
SO  - Thromb Res. 2001 Aug 15;103(4):325-35. doi: 10.1016/s0049-3848(01)00314-0.