School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Bioorg Med Chem. 2013 Jul 15;21(14):4259-65. doi: 10.1016/j.bmc.2013.04.068. Epub 2013 May 6.
Luteinizing hormone-releasing hormone (LHRH) analogues are used extensively for the treatment of various hormone-dependent diseases. However, none of the currently marketed derivatives can be administered orally. Modification of peptide sequences by attachment of carbohydrate moieties is a promising strategy that may increase the metabolic stability of the target peptide and enhance its transport across cell membranes, subsequently improving peptide bioavailability. In this study, either the N- or C-terminus of the LHRH peptide was altered by attachment of carbohydrate moieties. Caco-2 cells were chosen as an in vitro model to investigate both the permeability and stability of the new LHRH analogues. Our findings show that conjugating sugar moieties to the N-terminus of the LHRH peptide significantly increased both permeability and metabolic stability of most of the modified LHRH derivatives.
促黄体生成素释放激素（LHRH）类似物被广泛用于治疗各种激素依赖性疾病。然而，目前市场上销售的衍生物都不能口服给药。通过在肽序列上连接糖基来修饰肽序列是一种很有前途的策略，它可以提高目标肽的代谢稳定性，并增强其穿过细胞膜的运输能力，从而提高肽的生物利用度。在这项研究中，通过在 LHRH 肽的 N-或 C-末端连接糖基来改变肽序列。选择 Caco-2 细胞作为体外模型来研究新的 LHRH 类似物的通透性和稳定性。我们的研究结果表明，将糖基连接到 LHRH 肽的 N-末端显著提高了大多数修饰后的 LHRH 衍生物的通透性和代谢稳定性。
