Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia

J Med Chem. 1990 Dec;33(12):3138-42. doi: 10.1021/jm00174a008.

Abstract

5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / drug therapy
  • Animals
  • Dipeptides / chemical synthesis
  • Dipeptides / pharmacology
  • Gels
  • Hemoglobin, Sickle / chemistry*
  • Humans
  • Mice
  • Motor Activity / drug effects
  • Structure-Activity Relationship
  • Tryptophan / analogs & derivatives*
  • Tryptophan / chemical synthesis
  • Tryptophan / chemistry
  • Tryptophan / pharmacology

Substances

  • Dipeptides
  • Gels
  • Hemoglobin, Sickle
  • 5-bromotryptophan
  • Tryptophan