title: Angiotensin II inhibitory peptide found in the receptor sequence using peptide array.
abstract: Peptide array consisting of hundreds of peptides spatially addressed and synthesized on a cellulose membrane support was used to screen ligand-inhibitory peptides. As a model, angiotensin II (Ang II), a significant peptide related to the treatment of cardiovascular diseases, was chosen as the target ligand. Peptide arrays covering the Ang II receptor type 1 sequence were prepared, and peptide domains with high affinity to the Ang II fluorescein conjugate were investigated. The peptide (VVIVIY) within the first transmembrane region exhibited the highest affinity to Ang II. The synthesized soluble VVIVIY peptide had an 84% inhibitory effect on Ang II-induced aorta contraction. These results indicate that our screening strategy utilizing peptide array is an effective approach for the peptide drug development.
authors.affiliation: Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.forename: Mitoshi
authors.initials: M
authors.lastname: Kunimatsu
authors.forename: Seigo
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D019793:Fluorescein / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D040081:Protein Array Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019793:Fluorescein