Biopharmaceutical Characterization Services

PTMs of proteins, referring to the covalent addition of functional groups or proteins, the regulation of the proteolytic cleavage of subunits and the degradation of the entire protein, which can increase the functional diversity of the proteome and impact their structure, stability, function, interacting partners, and localization within the cell. PTMs have a critical role in many cellular processes such as cellular differentiation, protein degradation, signaling and regulatory processes, regulation of gene expression, and protein-protein interactions. The most common PTMs can be phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis.

A protein isoform, or 'protein variant' ³ is a member of a set of highly similar proteins that are structurally heterogeneous and mainly formed by alternative splicing, charge variants, truncations, amino acid substitutions, polymorphism and post-translation modifications (PTMs). Protein isoforms have critical roles in various biological processes such as heart hypertrophy, autoimmune diseases, diabetes, and they impact thyroid pathological conditions which are closely related to various cancer. Besides, these changes can also significantly impact the stability and activity of protein products, even cause immunologically adverse reactions. Based on the significant role of protein isoforms in various stages in a number of pathologies, detection of the isoforms is supposed to be an efficient biomarker or therapeutic targets.

Glycosylation is the process of transferring glycans to specific amino acid residues on proteins and proteins under the action of related enzymes to form glycosidic bonds. Biology glycosylation represents the enzymatic process in which glycans are attached to proteins, lipids, or other organic molecules. It has a vital effect on a wide range of biological processes such as cell attachment to the extracellular matrix and protein-ligand interactions in the cell. Besides, glycans produced by glycosylation are also essential in membrane and secreted proteins for their various structural and functional roles. Glycosylation analysis is an invaluable tool for biopharmaceutical development, control of protein biological functions, pharmacokinetics, antibody effector functions and biomolecular interactions.

The biosynthesis of protein begins at the N-terminal, the sequence composition of N-terminal plays an important role in biological functions of proteins and peptides. In scientific research, N-terminal sequencing can provide significant information for unknown or uncertain proteins. N-terminal sequences have a huge impact on the half-life of proteins and the localization in the subcellular organelles of proteins. What's more, a variety of post-translational modification will occur at the N-terminal, which is also associated with the function, properties and stability of proteins.

Disulfide linkage is a single covalent bond that formed between the sulfur atoms of cysteines. It is a relatively stable covalent bond that acts to stabilize the spatial structure of the peptide chain in proteins and is an important structural feature of many proteins. At tertiary structure level, disulfide bonds are formed inside the protein subunit, in contrast, the disulfide linkages are formed between two protein subunits at quaternary structure level, which has an important effect on biasing protein towards the folded topology.

Biomarker is an indicator that can objectively measure and evaluate normal biological processes, pathological processes, or response to drug intervention, and is also an important early warning indicator when organisms are damaged, involving changes in the structure and function of cellular molecules, and changes in biochemical metabolic processes. Due to the constant introduction of various top-notch techniques and methods such as proteomics, genomics, and neuroimaging, the scope of application of biomarkers has been expanded from the early diagnosis of disease to the monitoring of disease progression and evaluation of drug efficacy.

Ligand binding assays represents the process of quantifying an analyte for a ligand, which relies on the binding of ligand molecules to antigens, receptors, antibodies and other macromolecules. The main aspects of ligand-receptor binding interactions include binding affinity and kinetics, conformations of targets, binding thermodynamics and ligand efficiency. Based on the significant role of binding affinities and selectivity in evaluating the efficacy and safety for therapeutic antibodies, ligand binding assays are critical to the pharmacology for creating drugs that are able to mimic the endogenously found cellular components.

Polymer-drug conjugates (PDCs) are the systems formed by covalently linking polymer with one or more drug molecules directly or through a spacer. As an excellent drug delivery system, PDCs can signally increase the therapeutic index, prolong circulation of drug substances, enhance the accumulation of drugs in nidus and lead to sustained drug release. In this case, PDCs have been widely used in treatment of diseases especially for cancer and a number of PDCs are currently under clinical trials.

Antibody-drug conjugates (ADCs), the antibodies chemically linked to biologically active small molecule drugs, represents a new class of biotherapeutics that have a rapidly growing portion of the drug discovery pipeline in pharmaceutical companies. Drug/Antibody Ratio (DAR) is defined as the average number of drugs conjugated to the antibodies and is an important attribute of ADCs, which has an obvious effect on the efficacy of drug products. For example, low drug loading can lead to a reduced potency while high drug loading is closely related to toxicity and inferior pharmacokinetics.