Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia.
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.
De Croos
P Z
PZ
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60680.
Sangdee
P
P
Stockwell
B L
BL
Kar
L
L
Thompson
E B
EB
Johnson
M E
ME
Currie
B L
BL
D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy; D000818:Animals; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D005782:Gels; D006451:Hemoglobin, Sickle / Q000737:chemistry*; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D004151:Dipeptides; D005782:Gels; D006451:Hemoglobin, Sickle; C066614:5-bromotryptophan; D014364:Tryptophan