SYNTHESIS OF NOVEL TRIAZOLE-DERIVED GLYCOPEPTIDES AS ANALOGS OF a-DYSTROGLYCAN MUCINS

摘要

a-Dystroglycan (a-DG) mucins are essencial for maintenance of the structural and functional stability of the muscle fiber, besides being expressed in other tissues such as neural and epithelial. They are constituted by enriched serine/ threonine peptide sequences linked to the tetrasaccharide motif Neu5Aca2-3Gal(31-4GlcNAcss1-2Mana-O-Ser/Thr. When hypoglycosylated, a-DG mucins are directly involved in pathological processes such as dystroglycanopathies (Congenital Muscular Dystrophies-CMDs) and epithelial tumors, due to defective interactions with extracellular matrix proteins, such as laminin [1]. Thus, a-DG mucins are considered valuable targets for development of new therapeutic and diagnostic strategies against CMDs and cancer. Within this context, this work presents the synthesis of the novel 1,2,3-triazole-derived glycopeptides NHAcThrVal[aGlcNAc-1-triazol-2Mana]ThrlleArgGlyOH(1) and NHAcThrVal[Gal-pi,4-aGlcNAc-1-triazol-2Mana]ThrlleArgGlyOH (2) as analogs of a-DG mucins (Fig. 1).