PRISM BioLab Blog – PPI Pursuit
Commentary on Protein-Protein and Protein-Peptide Interactions, peptidomimetics and related topics in drug discovery.

Peptides exert high biological activity and specificity toward the target protein and sometimes accumulate in a particular tissue or organ owing to the transporter selectivity. Peptide-based drugs are aiming for smart utilization of the advantages and the conquest of disadvantages of peptides. Here is an interesting paper on hybrid molecules with peptides for...

Now the time to revisit fragment-based drug design (FBDD) in the age of artificial intelligence (AI). The popularity of FBDD has expanded over the past decade owing to the aid of the computational methodology development, the computer spec enhancement and the improved experimental environment. In spite of the world-wide, intensive research by both industry and academia, FBDD has not matured into the crucial breakthrough...

Oral bioavailability is a long-lasting issue on drug development. No one would doubt it as a breakthrough if human oral bioavailability is calculated by the molecule’s chemical structure in high accuracy. Lipinski rule-of-five¹⁾ is a rule-of-sum idea to design and choose drug-like molecules with reasonable bioavailability. However, it is not a golden rule and some drugs out-of-criteria are on the market as bioavailable drugs...

Machine learning is solving issues of extreme difficulty in extensive fields. In drug discovery and development, pharmacokinetics prediction is a have been the major target for building up the learning model with high accuracy. As a small molecule-based drug discovery company, we are intensive interest in creation of orally available drugs for user-friendliness. Oral bioavailability...

Intensive investigation has been conducted in order to rationally identify the “hotspot” of PPI for a decade or even more. In spite of the presence of a myriad of PPI in human, estimated to be 130,000¹⁾ to 650,000²⁾ This issue originates from the difficulty in controlling and modulating the PPI of interest by a small molecule. Generally speaking, the contact area of a small molecule inhibitor is thought to be 300 to 1,000 Ų⁾.³⁾

Conformational restriction has long been recognized in medicinal chemistry as a rational and effective way for structural design in both drug discovery and optimization stages. This strategy is crucial in PPIs in order for overcoming the energetical inferiority against the original, large-surface-based contact. The exception might be the biomolecule drugs like antibodies which recognized the protein...

Protein-protein interaction network is invaluable resource for the identification of a promising target for PPI drug research and development. Owing to the human genome sequencing and proteome analyses as well as the data science companies and organizations, we have rich access to PPI databases to figure out a candidate interaction to deeply investigate for a better treatment of diseases of worldwide interest. But still, it’s a kind of “mystery”...

Peptide-based molecules and peptides themselves, especially cyclic and natural peptides, have been approved for a variety of disease treatments including cancers.¹⁾ Anti-cancer peptides (ACPs) have long been investigated in mostly academic field and a number of natural ACPs have been disclosed so far.²⁾ ACPs are small peptide with a selective toxicity against cancer cells line a usual small-molecule-based or antibody-based anticancer agents...

PPI databases unambiguously expands our opportunity to figure out a fruit for a PPI drug target. Currently, more than twenty databases can be utilized for the sake of PPI research and predictions. One of the topmost databases on PPI is, generally speaking, STRING. PPI scientists usually takes STRING as one of the reliable, versatile and useful PPI database, but have you ever thought why STRING? Emerging PPI databases may also be worth looking at...

This review¹⁾ summarizes the recent status of peptide-based therapeutics research in the discovery stage and peptide related technologies in a simple fashion. It helps scientist in a variety of levels to achieve better understanding of peptide drug discovery issues as well. Peptides are among the classical and ubiquitous chemical types in the small-molecule world. Distinct and attractive nature of peptides...