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Abstract

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  2. Abstract
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The biological activities of chemically synthesized leukotriene B4 and eight structural analogues have been studied using chemotaxis, lysosomal-enzyme release and receptor-binding assays on human neutrophils. The results show that increasing the number of double bonds between C14 and C20, having triple bonds at C6 or C14, substitution of the primary carboxyl group at C1, changing the geometry of the double bond at C6 from the cis to trans configuration and changing the chirality of the hydroxyl group at C12 from the R to the S configuration result in substantial loss of both biological activity and the capacity to bind to the LTB4 recognition site in parallel. We suggest that the functional epitopes of 5S, 12R-dihydroxy-6, 14-cis-8, 10-trans-icosatetraenoic acid (LTB4) are either the same, or reside in the same domain as the binding site for the LTB4 receptor. Development of LTB4 antagonists to the high-affinity LTB4 receptor, based on the structure of LTB4, is unlikely to be successful.

Abbreviations
PMN

polymorphonuclear cells

HPETE

hydroperoxyicosatetraenoic acid

LTA4

5,6-oxido-7,9,11,14-icosatetraenoic acid

diHETE

dihydroxyicosatetraenoic acids

DMA

dimethylamide

LTB4

5S, 12R-dihydroxy-6, 14-cis-8,10-trans-icosatetraenoic acid (compound 1)

LTC4

5S-hydroxy-6R-glutathionyl-7,9-trans-11,14-cis-icosatetraenoic acid

IC50

concentration at which half of the response is inhibited

fmet

formylmethionyl

HBSS

Hanks' balanced-salt solution

HPF

High-power field

compounds I–IX

the structures and chemical formulae are shown in Fig. 1

REFERENCES

  1. Top of page
  2. Abstract
  3. REFERENCES