The invention belongs to the field of biological medicines, and provides a preparation method and application of a
stapled peptide and micromolecular antitumor
drug covalent conjugate with high stability and strong
antitumor activity. Traditional micromolecular antitumor drugs such as
camptothecin,
chlorambucil and the like have the problems of low water
solubility, low
bioavailability, poor stability,
drug resistance and the like. The
camptothecin or
chlorambucil is covalently coupled with the
stapled peptide through AEA, so that the water
solubility of the
small molecule medicine is remarkably improved, the anti-tumor onset time is remarkably shortened, and the long-lasting tumor
cell proliferation inhibition capability is shown. Compared with linear
peptide, the stability of the
stapled peptide is remarkably improved, and a polypeptide
drug coupling strategy based on the stapled
peptide solves the problem of poor stability of polypeptide in a coupled drug on one hand, and provides a new thought for further development of classical anti-tumor drugs on the other hand.