Genosphere Biotechnologies

CUSTOM SERVICES FOR RESEARCH
CUSTOMER SERVICES
FOR RESEARCH

Technical notes - Custom peptides

Synthetic peptide librairy design

Peptides: an infinite combination of biocompounds from 20 natural building blocks and more

Nature’s strategy for constructing proteins involves using a relatively small number of amino acids to create a vast array of variable and adaptable molecules. Proteins are highly versatile and can mediate a wide range of specific molecular interactions. These interactions, whether between proteins or between proteins and other molecules, play essential roles in all physiological and pathological phenomena of life. By using a limited set of amino acids, nature has created an enormous diversity of protein structures and functions, allowing for the regulation and control of various biological processes. The ability of proteins to interact selectively and specifically with other molecules has also made them invaluable tools in biomedical research and drug development. Synthetic peptide libraries have emerged as a powerful approach to creating new peptides with a wide range of biological activities, further expanding the possibilities for developing new therapeutics and research tools.

Synthetic peptide libraries: Screening tool for your research

Since the first reported use of synthetic peptide libraries by Geysen and colleagues in 1984, the field of combinatorial peptide library synthesis and screening has grown significantly. While the phage displays libraries approach using genetically modified bacteriophages to display peptides has proven very useful, synthetic libraries can be designed to include non-natural amino acids and modifications, structural change (e.g. cyclisation), thus providing diversity and modularity in designing higher affinity ligands.  At Genosphere Biotechnologies we have been preparing these regular and modified libraries for many years and we have established two service packages:

(i) Specification: Basic screening-grade peptide library

For economical initial or large scale peptide screens.

(ii) Specification: Pure qualification-grade peptide library

For exploration studies and validation of identified target sequences.

Synthetic peptide libraries: identify your bioactive peptide

The evolution of chemical and biological technologies for the production of peptides and proteins has made it possible to mimic nature’s approach to constructing new peptide sequences that recognize specific targets. Peptides possess intrinsic variability in their sequences and a unique ability to recognize other molecules with specificity, making them ideal building blocks for the design of new active peptides for life science R&D.

By screening large numbers of diverse peptides using high-throughput assays, it is possible to identify peptides with desired activities and functions for a range of applications, from drug discovery to diagnostic assays.

This approach has revolutionized the field of peptide-based therapeutics and has opened up new opportunities for exploring the vast potential of peptides in life science research.  This approach has successfully identified antimicrobial peptides, opioid receptor antagonists, ligands for cell surface receptors, protein kinase inhibitors and substrates, T cell epitopes, peptides binding to MHC molecules, and peptide mimotopes of receptor binding sites.

Many approaches are documented and offered by Genosphere biotechnologies to meet your research project:

•Alanine scanning peptide library

•Truncation peptide library

•Mutational peptide library

•Cyclic peptide library

•Overlapping peptide library

•In vitro evolution peptide library

•Positional scanning peptide library

Overlapping Peptide Library

The overlapping peptide library can be used for linear and continuous epitope mapping, which in turn can be used to determine which part of a given protein or peptide contains the essential amino acids that contribute to its functionality. Characterised by two parameters, fragment length and number of lags, each library is generated by dividing the original protein or peptide into several equal-length, overlapping fragments, each 8-20 residues in size.

Typically, a peptide fragment must be at least six residues long to span an epitope. The shift number is the number of amino acid residues shifted between adjacent fragments and it reflects the degree of overlap.

By carefully selecting the shift number and fragment length, one can minimize the cost of the experiment while maximizing the value of the data. The number of offsets is usually chosen to be one third of the length of the fragment. In general, longer fragments are difficult to synthesize but the library generates fewer fragments.

Also, the fragments are more likely to span an epitope. The combination of a low offset number and a short fragment length generates the highest number of fragments, while the combination of a high offset number and a long fragment length yields the fewest number of fragments.

Overlapping peptide libraries have proven very useful in many applications. For example, the library may be used for the determination of T cell epitopes in the fields of infectious diseases and vaccine development.

• Geysen, H.M. et al. (1984). Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A. 81, 3998-4002
• Eichler J. (2005).  Synthetic peptide arrays and peptide combinatorial libraries for the exploration of protein-ligand interactions and the design of protein inhibitors. Comb Chem High Throughput Screen.  8, 135-43.
• Gruber, C.W. et al. (2010). Ligand-based peptide design and combinatorial peptide libraries to target G protein-coupled receptors. Curr Pharm Des. 16, 3071-88.
• Lu, S. et al. (2023). Disulfide-Directed Multicyclic Peptide Libraries for the Discovery of Peptide Ligands and Drugs. J Am Chem Soc. 145, 1964-1972.
• Ralets, I. et al. (2004).  Identification of neurite extension inducing peptides by means of soluble combinatorial peptide libraries. J Neurosci Methods 137, 61-9.
• Jabre, N.D. et al. (2011). A highly divergent approach for synthesis of metal-binding peptide libraries. J Org Chem. 76, 2273-6.
• Pinilla, C. et al. (2022).  Identification of B Cell and T Cell Epitopes Using Synthetic Peptide Combinatorial Libraries. Curr Protoc. 2, e378.
• Appel, J.R. et al. (1996). Exploring antibody polyspecificity using synthetic combinatorial libraries. Mol Divers. 2, 29-34.
• Pastor, M.T. et al. (2004). Design of bioactive and structurally well-defined peptides from conformationally restricted libraries. Biopolymers 76, 357-65.
• Zhang, H. et al. (2021). Cyclic peptide drugs approved in the last two decades (2001-2021). RSC Chem Biol. 3, 18-31.
• Beveridge, R. et al. (2020). A synthetic peptide library for benchmarking crosslinking-mass spectrometry search engines for proteins and protein complexes. Nat Commun. 1, 742.
• Falciani, C. et al. (2005). Bioactive peptides from libraries. Chem Biol. 12, 417-26.
• Real, E. et al. (2004). Antiviral drug discovery strategy using combinatorial libraries of structurally constrained peptides. J Virol. 78, 7410-7.

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