Chemistry Department, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montreal, QC H3C 3J7, Canada.
Chem Biol Drug Des. 2010 Jan;75(1):40-50. doi: 10.1111/j.1747-0285.2009.00913.x.
Incorporation of amino lactams into biologically active peptides restricts conformational mobility and may enhance selectivity and increase potency. alpha- and beta-amino gamma-lactams (Agl and Bgl), in both S and R configurations, were introduced into the growth hormone secretagogue GHRP-6 using a Fmoc-compatible solid-phase protocol relying on N-alkylation with five- and six-membered cyclic sulfamidates, followed by lactam annulation under microwave heating. Using this protocol in conjunction with IRORI Kan techniques furnished eleven new GHRP-6 analogs, and their binding affinity IC50 values on both the growth hormone secretagogue receptor 1a (GHS-R1a) and CD36 receptors are herein reported. The results indicate that selectivity towards one receptor or the other can be modulated by lactam substitution, typically at the Ala3 and the D-Phe5 positions.
将氨基酸内酰胺并入生物活性肽中会限制构象的灵活性，并可能提高选择性和增强效力。α-和β-氨基酸γ-内酰胺（Agl 和 Bgl），无论是 S 构型还是 R 构型，都通过依赖于 N-烷基化的 Fmoc 相容固相方案被引入到生长激素促分泌素 GHRP-6 中，该方案使用五元和六元环状磺酰胺酯，然后在微波加热下进行内酰胺环合。使用该方案和 IRORI Kan 技术提供了十一个新的 GHRP-6 类似物，并且报告了它们对生长激素促分泌素受体 1a（GHS-R1a）和 CD36 受体的结合亲和力 IC50 值。结果表明，通过内酰胺取代可以调节对一种或另一种受体的选择性，通常在 Ala3 和 D-Phe5 位置。
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