Study On Chemical Assembled Kahalalide C Analogues With Glucose And The Activity

Cyclic peptide compounds in the synthesis of anticancer drugs,promising research has attracted much attention.At present about the separation,synthesis and structure modification of cyclic peptides has become a research focus in this field.Kahalalides compounds are a class of cyclic peptide compounds which is separated from the green algae Bryopsissp and the mollusc Elysia rufescens eating this green algae.Kahalalide C a member of the Kahalalides family has very perfect pharmacological activities,especially in the aspect of anti-tumor.Kahalalide C parent structure is composed of two D-tyrosine,an L-arginine,an L-isoleucine and an L-threonine,formed a cyclic pentapeptide esters.Like many marine natural products having good biological activity,Its parent structure is a cyclic pentapeptide esters with a sixteen ring structure which comprises a L-threonine.Carbohydrates are a class of biological molecules with diversity in structure widely distributed in nature.They are essential to most forms of life and play key roles in varied cellular processes.Glycopeptides are glycosylated peptide compounds.The glucose moiety of glycopeptides has an important role in the molecular recognition process.Posttranslational glycosylation defects is closely related to these pathological conditions of cell transformation and malignant lesions,such as cancer,immune deficiency syndrome and so on.Research in the glycopeptide class of drugs has caused widespread concern,so synthesis of the glycopeptide compound having a specific structure is important.According to principles of drug design and Isostere,taking Kahalalide C as the mother nucleus,design a cyclic pentapeptide ester with a sixteen ring structure including L-phenylalanine,L-valine,L-leucine,L-threonine.Replacing phenylalanine with para-F,-Cl,-Br,-OMe phenylalanine,synthesys a series of Kahalalide C cyclic peptide ester analogues.On the basis,taking containing L-phenylalanine and containing 4-OMe-L-phenylalanine as a representative cyclic peptide ester,conducte on the chemical assembly of L-threonine amino exposed to investigate their efficacy.On the basis of the above work,glycosyl is introduced in to Synthesis of the glycosyl Kahalalide C cyclic peptide ester analogs and glycosylated Kahalalide C chain peptide ester analogs.A preliminary study on the determination of the biological activity of these compounds,the introduction of the glycosylation on Kahalalide C cyclic peptide ester analogues has influence on biological activity and water-soluble.