For these reasons, a combination of multiple biomarkers is preferred, which could result not only in improved accuracy, but also in the increase of a sample throughput and reduction of cost per test

For these reasons, a combination of multiple biomarkers is preferred, which could result not only in improved accuracy, but also in the increase of a sample throughput and reduction of cost per test. in proteomics is rather difficult.14 This is in contrast to a very large amount WNT-4 cIAP1 Ligand-Linker Conjugates 3 of reviews on EC analysis of nucleic acids and particularly on sensors and arrays applicable in genomics, which appeared in the recent decade.15?36 Also, reviews on EC analysis of glycoproteins are rather scarce, limited mostly to promising EC impedance spectroscopic detection of lectin-captured glycoproteins.37?42 Wider application of EC analysis in proteomics and biomedicine was hindered until recently by the absence of a sensitive EC reaction applicable to thousands of proteins existing in nature. However, interfacial electrochemistry of conjugated proteins containing nonprotein redox centers (such as some metalloproteins) allowing direct (i.e., unmediated) and reversible electron transfer between electrode and nonprotein component greatly advanced in recent decades.43?48 The number of metalloproteins in nature is very large; unfortunately, only a very small fraction among them was shown to yield such reversible electrochemistry (see section 3 for details). To make methods of EC analysis more convenient for application in biomedicine and in the above -omics, advances in both label-free and label-based EC methods of proteins and carbohydrate components of glycoproteins analysis are desirable. In this Review, we wish to show that in recent years significant progress was done in the EC analysis of practically all proteins, based on the electroactivity of amino acid (aa) residues in proteins. Also, electrochemistry of polysaccharides, oligosaccharides, and glycoproteins greatly advanced in creating important steps for its larger application in the glycoprotein research. In recent decades, a great effort was devoted to the discovery and application of biomarkers for analysis of different diseases, including cancer.49?53 In the following paragraphs, special attention will cIAP1 Ligand-Linker Conjugates 3 be paid (i) to intrinsic electroactivity of peptides and proteins, including the sensitivity to changes in protein 3D structures (sections 4C6), as well as to recent advances in EC investigations of DNACprotein interactions (section 7), (ii) to intrinsic electroactivity of glycans and polysaccharides, advances in EC detection of lectinCglycoprotein interactions, and introduction of electroactive labels to polysaccharides and glycans (section 8), and finally (iii) to EC detection of protein biomarkers, based predominantly on application of antibodies in immunoassays, nucleic acid and peptide aptamers for construction of aptasensors, and lectin biosensors for detection of glycoprotein biomarkers (section 9). 1.1. Intrinsic Electroactivity of Proteins Since the beginning of the 1970s, EC analysis of proteins focused on reversible processes of nonprotein components in conjugated proteins. This very interesting electrochemistry was reviewed in numerous articles43?48 and will cIAP1 Ligand-Linker Conjugates 3 be here only briefly mentioned in connection to proteins cIAP1 Ligand-Linker Conjugates 3 involved in the DNA repair (section 7). At the beginning of the 1980s, it was shown that tyrosine (Tyr) and tryptophan (Trp) residues in proteins produced voltammetric oxidation signals at carbon electrodes.54?56 In the first decade after this discovery, the oxidation signals of proteins exhibited only low sensitivity, but later by using different carbon electrodes and EC techniques, these signals became more useful tools in electrochemical cIAP1 Ligand-Linker Conjugates 3 protein analysis (section 4) and were applied in biomedical research. Recently, a simple label-free chronopotentiometric stripping (CPS) electrocatalytic method has been introduced (section 5), allowing the determination of practically any protein at low concentration, as well as recognition of changes in the protein structures (section 5.3), including those resulting from a single aa exchange (point mutations). The protein structure-sensitive analysis requires very fast potential changes (taking place at highly negative current densities), which can be hardly obtained using the usual voltammetric techniques. Special properties of CPS in relation to protein analysis are discussed in sections 5.1C5.3. For protein structure-sensitive analysis, thiol-modified liquid mercury or solid amalgam electrodes are convenient (section 5.4). CPS appeared particularly useful in the analysis of proteins important in biomedicine (section 6), including tumor suppressor p53 protein (section 6.2) and its sequence-specific interaction with DNA (section 7.5). 1.2. DNACProtein Interactions Until recently, EC methods were little used in DNACprotein interaction studies and were not.