We offer physiologically active peptide design services including lead sequence, symmetric algorithm and the Protein & Hit Method (PH Method).
The principle of the PH Method
Analyses by our proprietary PH Method will identify peptide symmetry. We have found that a peptide’s symmetric properties correlate with peptide physiological activity.
In the PH Method, the elements of symmetry consist of the following three types:
The PH Method predicts that activity level can be higher in the absence of breaks in these three types of symmetry.
Here we explain the correlation between peptide symmetry and physiological activity using angiotensin as an example.
1. Angiotensin I is understood to have no effect on increasing blood pressure.
The PH Method algorithm identifies a symmetry break at His-Leu at the C-terminal end.
2. Angiotensin II is understood to have a more potent hypertensive effect than the other two peptides. The PH Method algorithm finds symmetry at both the N-terminal end and C-terminal end.
3. Angiotensin III is understood to have lower activity than angiotensin II.
The PH Method identifies a symmetry break at Ile, the 4th residue from the N-terminal end in the sequence of Arg-Val-Tyr-Ile-His-Pro-Phe-OH.
In this case, there is a symmetry break in the amino acid sequence in Arg-Val-Tyr and Ile-His-Pro-Phe-OH.
Such cases may result in multiple activities or lower activities.
For a design example employing the PH Method, these three residues, Arg-Val-Tyr, can be redesigned as a lead sequence, and then the sequence can be Arg-Val-Tyr-Met-Phe-Phe-Tyr-Phe-OH.
Then, the sequence can be estimated as a physiologically active peptide.
Peptide design by the PH Method will ensure symmetry in three types of sequences, N-terminal end, C-terminal end, and amino acid sequence.
Also we assume glucagon with unknown sequence (HSQGTFTSDYSKYLDSRRAQDFVQWLMNT), and if 6 residues HSQGTF constitute the lead sequence, we can design symmetrical sequence of HSQGTFTSDYSKYLDSRRAQDFVQWLMNT.
Our service can also design sequences HSQGTFTSDYSK which have fewer symmetry breaks.