Antisense-designed peptides: a comparative study focusing on possible complements to angiotensin II.
A comprehensive study of antisense peptides possibly complementary to angiotensin II (AII) is described. Antisense peptides of AII were designed using two different procedures outlined by Blalock and Root-Bernstein. Also, peptide complements designed to interact as homologs of AII were investigated. Three methods were used to detect binding between these peptides and AII. Several antisense-designed peptides were studied with unprotected termini to compare the effects of protected vs. unprotected termini. It was determined that the protected antisense-designed peptides derived from Root-Bernstein's methods interacted (high micro-molar range) directly with AII, while those protected antisense peptides derived from Blalock's method interacted only with the AII receptor. Two novel AII antagonists were discovered using this technology, a Root-Bernstein derived unprotected complementary peptide (H2N-K-G-V-Y-M-H-A-L-CO2H) and a Blalock derived unprotected antisense peptide (H2N-E-G-V-Y-V-H-P-V-CO2H), which exhibited 5 microM and 70 nM affinity toward the AII receptor, respectively.
Holsworth
D D
DD
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, MI.
Kiely
J S
JS
Root-Bernstein
R S
RS
Overhiser
R W
RW
D000311:Adrenal Glands / Q000378:metabolism; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D016376:Oligonucleotides, Antisense; D010455:Peptides; D012333:RNA, Messenger; D000804:Angiotensin II