The unfavorable conformational entropy change associated with folding into a unique structure can be decreased by preorganizing the desired structure. With the support of our advanced protein engineering platform established for many years, Creative BioMart has successfully used covalent cross-linking, synthetic templates or ligand binding to provide you with a fully customized knowledge-based preorganized structure design service.

Although the entropy cost of folding a single chain is lower than that required for modular intermolecular association, the cost of forming a unique three-dimensional structure from an unconstrained linear chain is still high. Furthermore, this strategy often lacks subtlety and can lead to misshapen and thus dysfunctional proteins. The researchers found that by using covalent crosslinks, synthetic templates, or ligand binding to pre-organize the desired structure, the unfavorable conformational entropy changes associated with folding into unique structures can be reduced. Linking peptide chains to synthetic templates is a non-native and efficient method by covalently constraining peptide chains to give them a specific structure. In addition, the introduction of ligand-binding sites (addition of metals such as Fe(II), Ni(II), Co(II), or Ru(II)) in secondary building blocks can also be used to drive the assembly of globular protein structures.

Fig 1. Protein stabilization by preorganization. (Ljubetič A, et al., 2017)

Services

De novo protein design and pre-organized structural synthesis play an important role in creating proteins with novel functions. Creative BioMart is committed to pre-organization by installing side-chain substituents that impose stereoelectronic and steric effects that limit backbone torsion angles and reduce conformational entropy changes. We provide various knowledge-based pre-organizational structure design services to global clients based on the following technologies:

• Covalent cross-linking.
• Synthetic template.
• Ligand binding.

For short peptide sequences (< 20 amino acids) to induce different levels of structural pre-organization, our solution is usually by introducing conformational constraints such as β-turn/loop template sequences and backbone cyclization. Depending on your project, our first consideration is the appearance of the metal ion binding sites and the number of coordination sites (donor atoms). Binding units (proteinogenic and non-proteinogenic amino acids and related amino acids) are then placed as needed to facilitate the desired range of coordination. For example, we engineered α non-native bivalent metal-binding moiety at the N-terminus of a short amphiphilic α -helix to induce self-assembly into a triple-helix bundle upon addition of metals such as Fe(Ⅱ), Copper(Ⅱ). We provide the most professional solutions for the design, synthesis and characterization of metal ion coordinated peptide scaffolds.

Service Principle

Creative BioMart is based on innovative, pragmatic and honest, adhering to the tenet of "Quality is our life, providing customers with the best quality service", providing customized services to customers around the world.

We will be glad to discuss details of intended interaction studies with you and develop experimental strategies/methods tailored to your requirement. Our customer service representatives are enthusiastic and trustworthy 24 hours a day, Monday to Friday. If you are interested in our services, please do not hesitate to contact us for more information or to discuss in detail.

Reference

1. Shoulders M D, Satyshur K A, Forest K T, et al.. (2010) Stereoelectronic and steric effects in side chains preorganize a protein main chain[J]. Proceedings of the National Academy of Sciences. 107 (2): 559-564.

• Knowledge-Based Membrane Protein Design
• Knowledge-Based Novel Protein Folds Design
• Knowledge-Based Secondary Structure Self-Assembly Design
• Knowledge-Based Single-Chain Protein Design