Solution synthesis of human peptide YY (hPYY)

Area of Science:

• Biochemistry
• Pharmacology
• Endocrinology

Background:

• Peptide YY (PYY) is a gastrointestinal hormone involved in regulating appetite and energy balance.
• Understanding the synthesis and biological activity of human PYY (hPYY) is crucial for potential therapeutic applications.

Purpose of the Study:

• To synthesize human peptide YY (hPYY) using a conventional solid-phase peptide synthesis approach.
• To evaluate the biological activity of synthetic hPYY in a canine model, comparing it to porcine PYY.

Main Methods:

• Peptide synthesis involved assembling six peptide fragments followed by deprotection using trimethylsilyl trifluoromethanesulfonate (TMSOTf) and thioanisole in trifluoroacetic acid (TFA).
• Purification was achieved through gel-filtration on Sephadex G-25 and subsequent reversed-phase high-performance liquid chromatography (RP-HPLC).
• Biological activity was assessed in dogs by measuring effects on systemic arterial blood pressure and splanchnic blood flow.

Main Results:

• A highly purified sample of synthetic hPYY was obtained after rigorous purification steps.
• Synthetic hPYY exhibited comparable biological activity to synthetic porcine PYY in dogs.
• The observed effects were related to systemic arterial blood pressure and splanchnic blood flow regulation.

Conclusions:

• The study successfully established a method for synthesizing highly purified human peptide YY (hPYY).
• Synthetic hPYY possesses biological activity in vivo that is similar to its porcine counterpart.
• These findings support the potential use of synthetic hPYY in further physiological and pharmacological studies.