Affiliation:
1. Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow,Russian Federation
Abstract
:
Abstract: Cancer is one of the leading social problems of the modern world. Today prostate cancer is
the second leading cause of cancer deaths among men. Targeted drug delivery is widely used to treat
and diagnose prostate cancer. Conjugates selectively binding to prostate-specific membrane antigenbased
on urea ligands are being actively developed against this disease. The linker has a significant
influence on the biological activity of such conjugates. The linker performs a large number of functions,
and its modification is one of the key methods for creating the best pharmacological profile. This
review aims to discuss and analyze the main approaches to the method of introduction and synthesis of
linkers for this type of conjugates without a description of the influence of biologically active molecules,
as well as to establish the key modification methods that have a significant role on the structureactivity
relationship. For this purpose, a review of the current scientific literature was performed, both
for the conjugates under development and those already undergoing clinical trials. It was found that the
optimal structure is a linker containing an aliphatic fragment near the vector-molecule (n(CH2) = 3-6),
followed by a polypeptide chain consisting of 2 to 4 amino acid residues. The presence of a Phe-Phe
dipeptide chain or the introduction of negatively charged groups also has a positive effect. Ongoing
research in this field helps to establish the accurate effect of each linker fragment, and the development
of solid-phase synthesis methods makes it much easier to achieve this goal.
Funder
Russian Foundation for Basic Research
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
8 articles.
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