Synthetic strategies in construction of organic low molecular-weight carrier-drug conjugates

Abstract

Inefficient transportation of polar metabolic inhibitors through cell membranes of eukaryotic and prokaryotic cells precludes their direct use as drug candidates in chemotherapy. One of the possible solutions to this problem is application of the 'Trojan horse' strategy, i.e. conjugation of an active substance with a molecular carrier of organic or inorganic nature, facilitating membrane penetration. In this work, the synthetic strategies used in rational design and preparation of conjugates of bioactive agents with three types of organic low molecular-weight carriers have been reviewed. These include iron-chelating agents, siderophores and cell-penetrating peptides. Moreover, a less known but very promising "molecular umbrella" conjugation strategy has been presented. Special attention has been paid on appropriate linking strategies, especially these allowing intracellular drug release after internalisation of a conjugate.

Keywords: Cell-penetrating peptides; Drug delievery; Molecular carrier-drug conjugates; Molecular umbrellas; Siderophores; Synthesis.