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Peptide Reference Desk

PYY(3–36) vs PYY(1–36): two missing residues change the receptor profile

DPP-4 removes the N-terminal Tyr-Pro dipeptide from PYY(1–36), producing PYY(3–36) and shifting receptor selectivity and analytical requirements.

PYY 3-36 archive searchResearch Use OnlyMetabolic Peptides

The processing step is the key fact

PYY is secreted as a 36-residue amidated peptide. DPP-4 removes the N-terminal Tyr-Pro dipeptide to generate PYY(3–36). The products differ by only two residues, yet the processing changes receptor preference: PYY(1–36) engages several Y-receptor subtypes, whereas PYY(3–36) is more selective for Y2.

An assay must distinguish the forms

“Total PYY” and “PYY(3–36)” are not interchangeable measurements. Immunoassay cross-reactivity, ex-vivo DPP-4 activity and sample-handling delay can alter the apparent ratio after collection.

Control pointWhy it matters
Protease inhibitionLimits conversion during sample handling
Form-specific calibrationSeparates total from active-form reporting
LC-MS resolutionConfirms the two-residue mass difference
C-terminal amidationPart of the declared molecular identity

Do not call one simply “the active PYY”

Activity depends on receptor, tissue and experimental question. PYY(3–36) is prominent in appetite literature, while PYY(1–36) retains broader receptor pharmacology. The professional record names the form rather than relying on a context-dependent adjective.

Verify with primary records

Use the primary paper, current regulator label or lot-linked analytical file for the claim it supports. A search result is a route to evidence, not the evidence itself.

Research-use reference only. No dosing, administration, compounding or human-use guidance is provided.