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Screening and design of functional peptides through application of bioinformatic analysis

  • Innovative Research Center for Preventive Medical Engeering

Hiroyuki Honda [Professor]

http://www.nubio.nagoya-u.ac.jp/proc/

Outline of Seeds

(Objective)
Extraction of sequence rules enabling the search for functional peptides. The search for functional peptides is a very effort- and time-consuming task because there are more than 64 million types of sequence variations in a peptide of just 6-mer. Therefore, we focused on amino-acid residues that form peptides and using an information processing method developed separately, we aim to extract peptides based on the principle of discovering what makes functional peptides functional. In this method, because functional peptides can be identified based on their functionality, a no-miss technique for peptide screening is possible. If this intellectual property can be secured as a set of rules, this would be an important addition to any research arsenal. Eventually, it could lead to rapid screening technology for peptide drugs and peptide food additives leading to a major breakthrough in the field of pharmaceutical, food, cosmetic and other industries.
(Overview)
Our research is focused on searching for functional peptides with the use of peptide-array production technology that successfully arrays of peptides on solid surfaces such as cellulose film or glass plates using a solid phase synthesis method. By promoting confluent composition, at present it is possible to successfully array around 1000 types of peptides. The peptide arrays thus produced are evaluated for their functions using biological molecules such as target protein or cells as such. The number of bonds between two peptides can also be obtained as exhaustive data using biomolecular interaction analysis equipment. It is also possible to search for intracellular functional peptides as well as perform functional analysis of free peptides released by the use of photocleavage linkers. The correlation between peptide array and function can be modelled by inputting the data related to peptide sequence and function into the information processing method. Rather than the array (or sequence) itself, hydrophobicity or electrostatic interactions are used as numerical data for a quantitative matrix and so on. Focusing on the position of the amino acid residues that constitute a peptide, the size or the charge of the side chain, and physicochemical properties such as hydrophobicity; if cause-effect modelling can be performed from a sufficient amount of peptide sequence information, the sequence of peptide possessing the function of interest can be extracted in principle. For example, if the amino acid at residue 1 of N-terminal has a bigger size and the one at residue 4 has small charge, they possess the function of promoting cell adhesion as a rule. By searching from among the sequences that meet this rule, the search process can be accelerated and more effective for obtaining intellectual property related to highly effective peptides. Furthermore, with the use of this model, we can be able to predict the binding sequences of unknown peptides.

Novelty and originality of this research

With respect to the peptide array, by investigating the interaction with the biomolecules or cells focusing mainly on proteins, we can collect numerical data on function of individual peptides. In this way, it differs from the positive selection methods such as phage display.
Although the data regarding peptide functions are being accumulated, there is no way to extract the cause-and-effect relationship in the interaction as a rule. By using our approach, first, a method to explore the sequences of peptide that interact with a novel peptide can be constructed. We have already succeeded in extracting the rules for peptide sequences involved in cellular adhesion, recognition of nanoparticles and inhibition of cholesterol absorption.

Application and research area for Industry collaboration

(Product Image)
Discovery of peptides as lead compounds of pharmaceutical products. Discovery of functional peptides for food. Discovery of novel peptides for cosmetics and other biochemical industries.
(Ripple effect on local economy)
The famous molecular antibody drug Herceptin alone recorded a sales of more than 400 billion yen. Accordingly, if a discovery of a suitable peptide drug can be made, comparable financial implications can be expected.
(Prospects for practical application)
Introduction of a suitable application that needs discovery. Construction of efficient screening system. Development of a glass slide based search tool.

Keywords

Peptides, search, information analysis, sequence information, functional biomolecules, life sciences/ drug discovery and diagnosis