Antisense homology box-derived peptides represent a new class of endothelin receptor inhibitors.
Several peptides encoded by the sense and corresponding antisense DNA have been found to recognize and bind to each other. We developed software to search for sense-antisense regions within proteins taking into account the degeneracy of the genetic code, i.e., one amino acid can have several "antisense" counterparts. Using this approach, we searched endothelin receptor type A for intramolecular regions related in sense-antisense fashion. After locating these regions (termed "antisense homology boxes"), several corresponding peptides were synthesized. The four new ET(A) receptor fragment peptides ETR-P1 ("CALSVDRYRAVASW"), ETR-P3 ("QGIGPLITAIEI"), ETR-P4 ("IADNAERYSANLSSHV") and ETR-P6 ("LNRRNGSLRIALSEHLKNRREVA") reported here can inhibit ET-1 activity.
Baranyi
L
L
Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan.
Campbell
W
W
Ohshima
K
K
Fujimoto
S
S
Boros
M
M
Kaszaki
J
J
Okada
H
H
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D016373:DNA, Antisense / Q000235:genetics*; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D010449:Peptide Mapping; D010455:Peptides / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012984:Software
D016373:DNA, Antisense; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010455:Peptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D002118:Calcium