One-Stop Solution for Anti-PTM VHH Antibody Development

Creative Biolabs has been long-term devoted to the development and application of single domain antibody (sdAb). SdAb is an artificially designed antibody molecule, also known as VHH antibody or camelid antibody. To fill the gaps in the field of PTM identification and detection, our scientists have built one-stop solutions for anti-PTM VHH antibody development for our clients all over the world.

Discovery and Development of Novel Anti-PTM VHH Antibodies

Post-translational modification (PTM) refers to the covalent and generally enzymatic modification after the protein translation. It usually occurs on the amino acid side chains or at the C- or N-termini of proteins with over 30 different classes (e.g., glycosylation, phosphorylation, and methylation). These various PTMs play key roles in a series of cellular processes, such as cell signaling, regulation of gene transcription, and protein degradation. These processes modulate the physical and chemical properties, conformation, folding, stability, and activity of proteins, thereby modifying the functions of proteins and even may lead to cancer. In this case, the identification and detection of PTMs are critical for understanding cell biology as well as disease mechanisms and further manipulating the biological mechanisms of proteins.

Currently, characterization of PTMs heavily relies on proteomics analyses and anti-PTM antibodies have served as an essential component for detecting and enriching PTMs. Consequently, the discovery and development of highly specific and potent antibodies to PTMs become very urgent to meet the needs of the market. Single domain antibodies have now become a better option than conventional antibodies for PTM recognition because of their unique properties of smaller size (~ 15 kDa) and better penetrability. VHHs are expected to recognize PTM sites more specifically, which can improve the efficiency of identifying the target PTM and reduce background caused by cross-reaction. With over ten years of extensive experience, Creative Biolabs can provide customized solutions to generate high-specific VHHs for different PTM sites.

Typical Pathway for PTM-specific VHH Antibody Development

Features of One-Stop Anti-PTM VHH Antibody Development

Creative Biolabs is a leading service provider that focuses on novel VHH discovery and development. We are pleased to share our extensive experience and advanced platform to satisfy each of your specific demands. If you are interested in generating high-specific anti-PTM VHHs, please do not hesitate to contact us for more details.

Published Data

Fig. 1 Development and Analysis of Immunized Camelid's Serum for VHH Identification.^{1, 2}

This study examines the potential of a selective VHH to target 3-nitrotyrosine (nitroTyr) modified proteins, which is a crucial step in developing therapeutics for oxidative stress-related diseases. The researchers synthesized several nitroTyr-modified 14-3-3 signaling proteins using genetic code expansion (GCE) and immunized an alpaca with these nitrated immunogens to generate VHHs that specifically target nitroTyr-proteins. Following the library generation and phage display selections, they successfully identified a specific VHH, Nb-G5. Nb-G5 displays selective recognition of nitroTyr-modified 14-3-3 proteins even in highly proteinaceous solutions. In this proof-of-concept study, researchers create a VHH that is highly selective for a 3-nitrotyrosine (nitroTyr) modified version of the 14-3-3 signaling protein, with decreased recognition of nitroTyr in other protein settings. This advancement paves the way for the GCE-facilitated development of more anti-PTM VHHs.

FAQ

1. What are anti-PTM VHH antibodies?

Anti-PTM VHH antibodies are single-domain antibodies that identify and bind to proteins with post-translational modifications. PTMs include phosphorylation, methylation, acetylation, ubiquitination, and glycosylation, among others, which occur after proteins are synthesized. These alterations can have an impact on protein function, stability, localization, and interactions with other molecules. VHHs, sometimes called single-domain antibodies or nanobodies, are the smallest functional antibody fragments generated from camelid antibodies.

2. Why are VHH antibodies particularly suitable for targeting PTMs?

VHH antibodies are ideal for targeting PTMs because of their small size (~ 15 kDa), excellent stability, and durability in many circumstances. This enables them to access and recognize epitopes in proteins that are typically inaccessible to the bigger conventional antibodies. VHH antibodies are highly specific and effective at differentiating between modified and unmodified proteins.

3. How can anti-PTM VHH antibodies contribute to personalized medicine?

In tailored therapy, anti-PTM VHH antibodies provide different methods for identifying and measuring PTMs, which differ from person to person and from disease to disease. It can help diagnose diseases more accurately, track disease progression more precisely, and tailor treatments to people's molecular profiles. Anti-PTM VHH antibodies could also be used to develop tailored treatments that target aberrant PTMs that are associated with specific illnesses.

4. What is the impact of anti-PTM VHH antibodies on the study of proteomics?

Anti-PTM VHH antibodies have a significant impact on proteomics since they are extensively used for studying PTMs within the proteome comprehensively. They also enable precise mapping and quantification of PTMs on proteins, improving our understanding of their functional role in cellular processes. This can help investigate and uncover new biomarkers and therapy targets while also clarifying disease mechanisms.

5. What future developments can be expected in the field of anti-PTM VHHs?

In the future, anti-PTM VHHs are expected to be discovered with more accuracy in a shorter period, including advances in computational modeling and artificial intelligence to predict high-affinity binding domains. Additionally, their applications can be broadened by both improving humanization methods to minimize immunogenicity for therapeutic use and expanding the range of detectable PTMs. Integration with advanced imaging technologies and novel delivery systems for in vivo applications could revolutionize both research and clinical diagnostics.

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