Pyridoxal derivative for pegylation modification of N terminal of protein and preparation method and application thereof

Abstract

The invention overcomes the problems of long reaction time and low yield of the existing transamination method involving pyridoxal, and provides a designed and synthesized pyridoxal derivative for improving the transamination efficiency of N-terminal amino acid of protein, particularly the high-steric hindrance amino acids such as leucine, isoleucine, and valine. The pyridoxal derivative is characterized by having a structure shown by the formula VIII. The pyridoxal derivative disclosed by the invention improves the transamination efficiency of the N-terminal amino acid of the protein, particularly the transamination reaction of the polypeptide containing high-steric hindrance amino acids (Leu, Ile and Val) at N terminal, thereby being favorable for further pegylation modification of protein.

Description

technical field

[0001] The invention relates to the field of chemical synthesis and modification of protein, and relates to a novel pyrrole aldehyde derivative used for PEGylation modification of protein N-terminus, a preparation method and application thereof. Background technique

[0002] With the development of modern biotechnology, protein drugs develop rapidly. Especially with the completion of the Human Genome Project and the progress of proteomics research, more and more protein drugs will be used for disease treatment. However, these drugs have a short half-life in vivo due to rapid renal elimination and proteolysis. In order to maintain the efficacy of the drug, it is usually necessary to use high doses of protein drugs, which not only increases the cost of treatment, but also easily increases adverse side effects such as immune response. So far, the most successful means to solve the defects of protein drugs is to modify and shield the surface of proteins by cova...

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