World’s largest and most structurally diverse library of natural peptides.
Phylogica’s proprietary Phylomer® libraries contain billions of distinct peptides that represent a rich source of biologically active drug leads for a broad range of intracellular and extracellular disease targets. The Phylomer libraries are based on expressed sequences of protein fragments that are encoded by the natural genes of evolutionary diverse microbes that often exist in extreme environments. Typically, these peptides, which are known as Phylomer peptides, are comprised of 15 to 50 amino acids.
The inherent diversity of the genetic sources of Phylomer peptides means that libraries contain multiple classes of subdomain and supersecondary structures across thousands of distinct structural families. Phylomer peptides show excellent specificity and are high affinity disruptors of protein-protein interactions and binders of protein targets.
Since Phylomer libraries have the most comprehensive collection of distinct protein-based structures available this gives them a key versatility advantage over other libraries such as classes of antibody alternatives. This feature of high structural diversity has resulted in Phylomer libraries successfully yielding high quality functional primary hits (pM- nM affinity), against multiple classes of intracellular and extracellular drug targets as well as in direct phenotypic screens.
Phylomer libraries are available for drug discovery screening in various phage display and yeast-two-hybrid formats as well as in mammalian expression vectors for phenotypic screening.
Phylomer libraries have a number of advantages against a range of alternate random peptide screening technologies for biologic discovery. These include:
- Highest functional hit rates for peptides – 100-fold better at disrupting protein interactions than comparable hit rates obtained using random peptide screening technologies.
- Higher stability – many Phylomer peptide structures are derived from natural protein subdomains that are rigid but not constrained by disulphide bonds, therefore they could potentially remain in a stably folded conformation for binding even inside cells. This contrasts to many short random peptides which are often unstructured or linear and sensitive to degradation. Some Phylomer peptides also have inherent thermal stability.
- Greater structural diversity and most comprehensive collection of distinct protein-based structures – enables billions of individual clones from thousands of structural families to be sampled. While Phylomer libraries are a similar size to random peptide or antibody Fab fragment libraries, unlike proteins which have a single scaffold eg antibody Fab scaffold, Phylomer libraries represent diversity within multiple classes of protein scaffolds.
- Bio-informatic advantages – Phylomers are derived from fully sequenced microbial genomes, which allow easy analysis of Phylomer peptide hits and rapid clustering into structurally related families to inform Structure Activity Relationships (SAR).
Natural source of Phylomer peptides
The Phylomer peptide sequences were sourced from an evolutionary diverse range of microbes (Bacteria and Archaea) genomes. These microbes were often collected from diverse and harsh environments, where their genomes were subject to intense natural selection to evolve the most stable protein structures that facilitated their survival.
Phylomer libraries can be accessed through contract drug discovery partnerships.