Ascidiacyclamides containing oxazoline and thiazole motifs assume square conformations and show high cytotoxicity. (17th September 2018)

• Record Type: Journal Article
• Authors: Asano, Akiko; Yamada, Takeshi; Taniguchi, Taizo; Sasaki, Masahiro; Yoza, Kenji; Doi, Mitsunobu
• Is Part Of: Journal of peptide science. Volume 24:Number 10(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-17
• Subjects: 1H NMR -- ascidiacyclamide -- CD spectrum -- crystal structure -- cytotoxicity -- oxazoline -- thiazole; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3120
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Four cyclic octapeptides were designed from ascidiacyclamide [ cyclo (–Ile–Oxz–D ‐Val– Thz–)2 ] (ASC, 1 ) to investigate the effects of oxazoline (Oxz) and thiazole (Thz) rings on the structures and cytotoxicities of the peptides. cyclo (–Ile–Thz–D ‐Val–Oxz–)2 (2 ) had the same number of Oxz and Thz rings as ASC, but the ring positions were switched. cyclo (–Ile–Oxz–D ‐Val–Thz–Ile–Thz–D ‐Val–Thz–) (3 ) and cyclo (–Ile–Thz–D ‐Val–Oxz–Ile–Thz–D ‐Val–Thz–) (4 ) contained one Oxz and three Thz rings within the molecule. All Oxz rings were substituted with Thz in cyclo (–Ile–Thz–D ‐Val–Thz–)2 (5 ). These analogues had new Oxz and Thz blocks forming the 24‐membered ring. Based on CD spectra and X‐ray diffraction analyses, the structures of all four analogues were classified as square ASC forms. But the structures of2 and5 differed from the original square form of1, and they showed no cytotoxicity. The structure of3 was very similar to that of1, and3 showed 10 times greater cytotoxicity than1 . Although no definite structure of4 was obtained, it showed three times greater cytotoxicity than1 . It appears that the position and number of Oxz residues are essential determinants in the structure‐cytotoxicity relationship of ASC analogues. Abstract : We found that changing the positions of the five‐membered heterocycles altered the conformational equilibrium of ascidiacyclamid (ASC). It appears that the position and number of oxazoline are essential determinants in the structure‐cytotoxicity relationship of ASCs.