Journal articles

This work describes the assessment of a de novo synthetic affinity ligand for recombinant human erythropoietin (rHuEPO), based on the multicomponent Ugi reaction. Four Ugi ligands were designed based on the X-ray crystallographic structure of the complex between human erythropoietin and site 1 of its cell-surface receptor (EPObp)2 ; screening of the ligands with pure rHuEPO samples identified a lead ligand (A9C10I8) immobilized on aldehyde-functionalized agarose beads, which was able to bind and elute erythropoietin, as determined by SDS-PAGE and Western blot analyses.

Spores of Bacillus megaterium QM B1551 germinate rapidly when exposed to a number of single-trigger germinant compounds, including glucose, proline, leucine, and certain inorganic salts. However, spores of strain PV361, a plasmidless QM B1551 derivative that lacks the GerU germinant receptor (GR) responsible for mediating germination in response to single-trigger compounds, can germinate efficiently when incubated in nutritionally rich media, presumably via activation of additional germinant receptors.

This work reports the development of a synthetic affinity adsorbent for immunoglobulins based on the Fab-binding domain of Streptococcal Protein G (SpG-domain III). The ligand (A2C7I1) was synthesized by the four-component Ugi reaction to generate a substituted peptoidal scaffold mimicking key amino acid residues of SpG. Computer-aided analysis suggests a putative binding site on the CH 1 domain of the Fab molecule.

In vivo glucose monitoring is required for tighter glycaemic control. This report describes a new approach to construct a miniature implantable device based on a magnetic acoustic resonance sensor (MARS). A ∼600-800. nm thick glucose-responsive poly(acrylamide-co-3-acrylamidophenylboronic acid) (poly(acrylamide-co-3-APB)) film was polymerised on the quartz disc (12. mm in diameter and 0.25. mm thick) of the MARS. The swelling/shrinking of the polymer film induced by the glucose binding to the phenylboronate caused changes in the resonance amplitude of the quartz disc in the MARS.

In this report, the dielectric constant of glycerol solutions (0-70% (w/w)) and the mechanical transitions of poly(2-hydroxylethyl methacrylate-co-methacrylic acid) films (600-800 nm, 1.5-10 mol% cross-linker) have been investigated by the magnetic acoustic resonance sensor (MARS), which is an electrode-free acoustic sensor and operates over a continuous frequency spectrum (6-200 MHz). When a glycerol solution was loaded, the response of the MARS decayed exponentially as the operating frequency was increased.

Numerous efforts have been devoted to develop synthetic affinity ligands mimicking natural immunoglobulin-binding proteins, such as Proteins A and L, in order to overcome intrinsic drawbacks involving their high cost and acidic pH elution. However, few reports have focused on a Protein G mimic. This work describes the use of the solid phase multi-component Ugi reaction to generate a low cost, rationally designed, affinity ligand to mimic Protein G for the purification of mammalian immunoglobulins, including the heavy-chain only camelid IgGs, with effective elution at neutral pH.

In vivo glucose monitoring is required for tighter glycaemic control. This report describes a new approach to construct a miniature implantable device based on a magnetic acoustic resonance sensor (MARS). A ≈ 600-800 nm thick glucose-responsive poly(acrylamide-co-3-acrylamidophenylboronic acid) (poly(acrylamide-co-3-APB)) film was polymerised on the quartz disc (12 mm in diameter and 0.25 mm thick) of the MARS. The swelling/shrinking of the polymer film induced by the glucose binding to the phenylboronate caused changes in the resonance amplitude of the quartz disc in the MARS.

Protein phosphorylation is a complex and highly dynamic process involved in numerous biological events. Abnormal phosphorylation is one of the underlying mechanisms for the development of cancer and metabolic disorders. The identification and absolute quantification of specific phospho-signatures can help elucidate protein functions in signaling pathways and facilitate the development of new and personalized diagnostic and therapeutic tools.

The emergence of molecular biomarkers for psychological, psychiatric, and neurodegenerative disorders is beginning to change current diagnostic paradigms for this debilitating family of mental illnesses. The development of new genomic, proteomic, and metabolomic tools has created the prospect of sensitive and specific biochemical tests to replace traditional pen-and-paper questionnaires.

Affinity chromatography is the method of choice for biomolecule separation and isolation with highly specific target recognition; it is ideally suited to the purification of immunotherapeutic proteins (i.e., mAbs). Conventional affinity purification protocols are based on natural immunoglobulin (Ig)-binding proteins, which are expensive to produce, labile, unstable, and exhibit lot-to-lot variability. Biological ligands are now being replaced by cost-effective, synthetic ligands, derived from the concepts of rational design and combinatorial chemistry, aided by in silico approaches.