title: Improvement of biological activity and proteolytic stability of peptides by coupling with a cyclic peptide.
abstract: The cyclic moiety of an endothelin antagonist peptide RES-701-1, composed of 10 amino acids with an amide bond between alpha-NH(2) of Gly1 and beta-COOH of Asp9, was coupled to some biologically active peptides aiming to improve their activities and stabilities against proteolytic degradation. Coupling of the cyclic peptide to the N-terminal of RGD-peptides, maximally 4-fold improvement of in vitro activity compared to the original peptide has been achieved. Coupling of it to protein farnesyltransferase inhibiting peptides resulted to improve in vitro activity maximally 3-fold. These peptides coupled with the cyclic peptide also showed enhanced stability against some typical proteases. These results indicate that this cyclic peptide can stabilize the conformations of the peptides coupled to its C-terminus. Coupling of our cyclic peptide is anticipated to be a novel conformational stabilizing method for biologically active peptides, results to improve their activity and stability.
authors.affiliation: Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shibata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Soga
authors.forename: Tamio
authors.initials: T
authors.lastname: Mizukami
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hanai
authors.forename: Motoo
authors.initials: M
authors.lastname: Yamasaki
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D010450:Endopeptidases / Q000737:chemistry*; D016232:Endothelins / Q000037:antagonists & inhibitors; D051231:Farnesyltranstransferase; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D018631:ras Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D016232:Endothelins; D010455:Peptides; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; C087120:RES 701-1; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D010450:Endopeptidases; D018631:ras Proteins