Synthesis Of Cyclic RGD-Containing Pentapeptides And Study On The Activity As Integrin α_vβ₃ Antagonists （2）

Cyclic peptides are very important compounds. They exist widely in nature and show versatile bioactivities. And their antitumour activity is outstanding. So the research in this field is very hot. Sansalvamide A is a cyclic depsipeptide which was isolated from a marine fungus of the genus Fusarium by BELOFSKY in 1999. Sansalvamide A peptide shows difference activities, although the difference between them is only that the ester was changed to amide. Sansalvamide A peptide demonstrates 10 times greater potency than the natural product depsipetide against the human colon carcinoma.av(33 integrin receptor (herein referred toαvβ3 receptor) not only including in osteosarcoma, neuroblastoma, lung cancer, breast cancer, prostate cancer, bladder cancer, glioblastoma and invasive melanoma and other tumor cell surface has high expression and has a strong expression of endothelial cell membrane. A large number of experimental studies have confirmed that small molecules cyclicpeptides with a containing RGD sequences have strong activity by selectively inhibiting tumor cell adhesion and metastasis, and induced apoptosis of tumor neovascularization. One of Merck KGaA’s angiogenesis inhibitor Cilengitide (EMD 121974) (Ⅲ) was awarded a rare treatment of glioma patients eligible for drug treatment, which can inhibit glioblastoma (U87MG) and medulloblastoma (DAOY) transplanted tumor growth.This subject take me-too strategy, and the basis of previous studies, RGD and methyl tyrosine will be embedded into our cyclic pentapiptide, to synthesis 4 cyclic pentapeptide contain-ing RGD sequence and inspecte the activity of the influence when there is N-methyl amino acid as well as RGD order.In the study of synthetic molecules, our focus was on the preparation of N-methyl amino acids and elongation of the chain peptide and the conditions of cyclization reaction in the last. We synthesized a series of cyclic peptide molecules by convergent methodology in solution phase. All synthetic compounds were either purified by flash chromatography, and all synthetic compounds were confirmed by NMR and HRMS.