Shenbagamurthi P, Baffi R, Khan S A, Lipke P, Pousman C, Becker J M, Naider F
Biochemistry. 1983 Mar 1;22(5):1298-304. doi: 10.1021/bi00274a047.
Ten analogues of His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr, the dodecapeptide alpha factor of Saccharomyces cerevisiae, were synthesized by conventional solution phase techniques and purified by using high-performance liquid chromatography. The dodecapeptide was also synthesized attached at its carboxyl terminus to poly(ethylene oxide), a macromolecular protecting group. Analogues in which Lys6 or His1 was modified exhibited high biological activity as evidenced by their ability to elicit aberrant morphologies in a cells of S. cerevisiae. These results suggest that neither a free alpha-amine nor a protonatable side chain at position 6 is necessary for biological activity of the dodecapeptide alpha factor. Although Ala2- and Phe2-dodecapeptides were not biologically active, they competed with the natural alpha factor and several active analogues. Thus binding of the alpha factor is not sufficient to elicit a biological response; it appears that the side chain in position 2 is critical for triggering morphological alterations in a cells.
通过传统的溶液相技术合成了酿酒酵母十二肽α因子His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr的十种类似物，并使用高效液相色谱法进行纯化。还合成了在其羧基末端连接有聚环氧乙烷（一种大分子保护基团）的十二肽。其中Lys6或His1被修饰的类似物表现出高生物活性，这可通过它们在酿酒酵母α细胞中引发异常形态的能力得以证明。这些结果表明，对于十二肽α因子的生物活性而言，6位上的游离α-氨基或可质子化的侧链都不是必需的。尽管Ala2-和Phe2-十二肽没有生物活性，但它们能与天然α因子和几种活性类似物竞争。因此，α因子的结合不足以引发生物反应；似乎2位上的侧链对于触发α细胞中的形态改变至关重要。
