Synthesis and application of functional peptides as cell nucleus‐directed molecules in the treatment of malignant diseases

Abstract

The unique functions of biomolecules, including transport across biological membranes (e.g. the cell membrane, the nuclear envelope), modulation of protein function, gene transcription, reconstitution of the malignant transformation, and viral, bacterial and fungal activities underlie a high pharmaceutical potential. The development of combinatorial functional peptide modules in this important area has been slow, in contrast to the rapid development in the synthesis of small biopolymers. The conjugation of a short transmembrane transport peptide module with a cell nucleus address peptide module and with any substance is attractive for preparation of BioShuttle-based peptides because of the well-established automated synthesis of peptides. Variation of the different functional modules for drug targeting and the choice of substances can be combined to create novel bioconjugates with unique properties. This article provides an overview of previous work on the BioShuttle technology and outlines the promising use of this approach in combinatorial peptide synthesis and drug discovery.

A Peptide & Peptide Nucleic Acid Synthesis Technology for Transporter Molecules and Theranostics - The SPPS

“…Since successful drug delivery and targeting is a very complex problem, directed drug delivery is one of the most important goals of pharmaceutical research and development. This is illustrated and discussed in a review of the BioShuttle technology and outlines the use of combinatorial chemistry and SPPS in drug discovery 68, 69.…”

Transfection of Molecular Beacons in Microchannels for Single-Cell Gene-Expression Analysis

“…Physical methods, such as microinjection [17,18] and electroporation [19,20], involve temporary disruption of the cell membranes with physical stresses. The chemical methods, such as cationic lipids, cationic polymers [21][22][23] and translocation peptides [20,23,24], are to chemically modify the permeation properties of the nucleic acids. For microfluidics-based molecular beacon transfection, biochemical methods are preferred over physical methods to minimize the stresses on the cells and to transfect multiple cells simultaneously.…”

Characterization of a gadolinium-tagged modular contrast agent by element and molecular mass spectrometry

“…With the latter approach, MRI contrast enhancement can be extended to intracellular compartments. [32][33][34] For imaging of the cytosolic compartment a modular contrast agent was synthesized, comprising (i) a DTPA metal chelator, (ii) a 22 mer antisense (anti-myc) PNA, and (iii) a 16 mer transport peptide. A Lys-Lys bridge was used to link the DTPA and PNA modules via amide bonds, whereas the transport peptide and the PNA were connected by formation of a Cys-Cys disulfide bridge, as displayed schematically in Fig.…”

“…Fig. 4 illustrates the size-exclusion chromatographic separation of the complete DTPA-PNA-peptide construct, where 32 S, 34 S and 157 Gd were monitored on-line by ICP-MS.…”