Research On Chemical Assembly And Activity Of Cyclic Depsipentapeptide And Side Chains

Cancer has become a common health diseases,multiple diseases which affects people’s lives,the annual death toll is close to or exceeds the cardiovascular and cerebrovascular diseases,so the study of anticancer drugs has been very tight.Zygosporamide is a kind of marine natural products with cyclic peptide ester structure,its structure contains two L-phenylalanine,a L-leucine,a D-leucine,and an alpha hydroxy alien acid.Studies have found that it not only has inhibitory activity on a wide varieties of tumor cells,but also has antibacterial,antiviral activity,immunosuppression,and so on.Therefore we can study the synthesis of Sansalvamide A analogues,and make its structure to be further modified,in order to obtain better antitumor activity of cyclic peptide compounds.RGD is one of the short peptide sequence with high biological activity,but its resistance to digestion in the body and the ability to resist chemical show degradation;therefore make RGD peptides and cyclic peptide compounds that have stable structure for chemical assembly,to increase RGD stability,heighten cyclic peptide combined biological activity by passing both synergy.Carbohydrate compounds are widely distributed that have a variety of biological molecules structure,and they are very important to many life forms.Sugar and other biological molecules combine to form glycoconjugate by covalent bonding among,the sugar part not only in the biological information storage,transshipment,etc plays an important role,also affects the solubility of molecules and biological activity,etc.In drug research,glycosylation modification will improve the pharmacokinetic process,and increase bioavailability.Amino thiazole compounds have unique biological activities,the study found that many amino acids containing thiazole ring show the activity on the peptide compounds,especially on anti-tumor activity which has increased significantly.So it is very necessary to introduce the thiazole ring to ring peptide compounds,and study its biological activity.This task use Zygosporamide as lead compounds,according to new drug development with series of principles and electronic body principle,and reform it’s structure to design a new ring 5 peptide ester structure.By introducing-Br,MeO-groups to the four of phenylalanine,we can synthesize Zygosporamide cyclic peptide ester analogues.Based on this through the ring five peptides on bare serine amino resin is introduced into aspartic acid side chain,make chemical assembly with RGD,sugar,thiazole methylamine and synthesize three kinds of cyclic peptide analogues modified by side chains.Optimize the synthesis conditions of cyclic peptide ester,and study the different kinds of assembly method between cyclic peptide ester and active side chains.Determine the antitumor activity of these compounds to study the bioactive differences between cyclic peptide analogues and cyclic peptide modified by side chains.Preliminary discussion the influence of the biological activity of cyclic peptide ester compounds by modified side chains.