pe
pep-10499 v1 CC-BY-SA-4.0

Amylin fragment (8-37): lab research tool

A lab-only piece of amylin, a hormone the pancreas releases with insulin, used by scientists to study how amylin signals work in the body. Experimental, not an approved drug.

statussynthesized targetCALCR length30 aa refs6
status 4 / 5
prediction metrics boltz-2 2.2.1
ipTM0.803
pTM0.808
avg pLDDT58.6
ranking score0.630
STRUCTURE · PEP-10499 × CALCR
ranking0.630
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence30 aa
151015202530
ATQRLANFLVHSSNN FGAILSSTNVGSNTY
in the news 11 articles
overview readme

What this is

Amylin (8-37) is a 30-amino-acid fragment of human amylin — the pancreatic hormone co-secreted with insulin by β-cells. The full hormone is 37 residues long; this peptide drops the first seven, removing the Cys2–Cys7 disulfide loop that the intact hormone uses to engage its receptor. It is a research-tool peptide used in laboratory studies of the amylin receptor system, not a therapeutic. The stored sequence ATQRLANFLVHSSNNFGAILSSTNVGSNTY is the N-terminally truncated backbone; the full-length amylin from which it derives normally carries a C-terminal amide and the disulfide ring at its N-terminus, neither of which is present in this 8-37 form.

What it does

Amylin's receptors are not stand-alone proteins. They are heterodimers built from the calcitonin receptor (CTR, gene CALCR) and one of three receptor activity-modifying proteins (RAMPs), giving three distinct amylin receptor subtypes — AMY1, AMY2, and AMY3 — alongside the related CGRP and adrenomedullin receptors of the same family (Hay 2018). Truncated amylin fragments that lack the N-terminal disulfide loop, including the 8-37 form, are studied as ligands at these CTR/RAMP complexes, where the missing N-terminus changes how the peptide engages the receptor relative to the intact hormone (Lee 2016).

Mechanism

The calcitonin receptor is a class B (secretin family) G-protein-coupled receptor. Peptide ligands of class B GPCRs use a two-domain binding model: the C-terminal portion of the peptide docks into the receptor's extracellular domain, and the N-terminal portion then activates the transmembrane core. Amylin (8-37) retains the C-terminal recognition region of amylin but loses the N-terminal segment required for full receptor activation, which is the structural basis for its use as a probe of amylin receptor pharmacology (Lee 2016). The extracellular domain of CTR is itself sensitive to post-translational modification — N-glycosylation at Asn130 of the human CTR extracellular domain significantly increases peptide hormone affinity (Lee 2017), and assembly with RAMPs allosterically reshapes the receptor's ligand preferences across the calcitonin/CGRP/amylin/adrenomedullin family (Advances in Pharmacology 2020; Hay 2018).

Evidence

  • Human: No human clinical trials. This peptide is a research reagent, not a drug candidate with registered trials on ClinicalTrials.gov.
  • Animal: The broader CTR/amylin receptor system has been characterized in mouse genetics: global and osteoclast-specific deletion of the calcitonin receptor causes increased bone formation, and calcitonin signaling through CTR negatively regulates osteoclast expression of Spns2 (Keller 2014). CTR-null mice also show susceptibility to hypercalcemia, establishing a physiological role for the receptor in calcium handling (Davey 2008). These studies use the receptor, not amylin (8-37) itself, as the experimental handle.
  • In vitro: Receptor-pharmacology work on the calcitonin/amylin receptor family — including binding and signaling studies of truncated peptide ligands at CTR alone and CTR/RAMP heterodimers — underpins what is known about how fragments like amylin (8-37) interact with this receptor system (Lee 2016; Lee 2017; Hay 2018).

Regulatory status

  • US / EU: Not a marketed drug; no FDA or EMA approvals. Research-grade peptide only.
  • WADA: Not individually listed. The full-length amylin agonist pramlintide is a marketed drug in a different class; amylin (8-37) is a distinct research fragment and is not the same molecule.

Related peptides

  • Full-length amylin and the pharmacological amylin analog pramlintide — the agonist counterparts of this fragment at the AMY receptor family.
  • Calcitonin — endogenous ligand of the calcitonin receptor (CTR), the shared GPCR backbone of the AMY receptors (Hay 2018).
  • CGRP and adrenomedullin — sister peptides in the same calcitonin/CGRP family, signaling through CTR-like receptor (CLR) plus RAMP combinations (Hay 2018; Advances in Pharmacology 2020).

Open questions

  • How the absence of the Cys2–Cys7 disulfide loop quantitatively reshapes binding kinetics at AMY1, AMY2, and AMY3 versus calcitonin receptor alone is not resolved in the sources collected for this card.
  • Whether glycosylation state of CTR (Lee 2017) differentially affects affinity of truncated amylin fragments relative to the intact hormone is not directly addressed by the available references.
Hypotheses2 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-11

Is the front part of the amylin fragment too floppy to trigger the receptor, even though the back part still docks correctly?

If confirmed, it would suggest that adding a simple molecular clamp to stiffen the loose end could convert this research tool into a functioning amylin mimic, potentially useful for treating type 2 diabetes or obesity.

The hypothesis
The low pLDDT (58.6) of amylin(8-37) when bound to the CTR/RAMP complex reflects genuine disorder in residues 8-15 (ATQRLANF), which are normally structured by the disulfide ring in full amylin, and this persistent N-terminal disorder is the primary reason the fragment fails to activate the transmembrane domain rather than simple steric loss of the loop.
Why it’s plausible
Class B GPCR activation requires N-terminal peptide insertion into the TMD bundle. pLDDT=58.6 averaged over 30 residues implies significant regional disorder. Residues 8-15, freed from the rigid disulfide constraint of full amylin, likely remain unstructured even when the C-terminal portion docks the ECD, preventing the conformational handoff needed for G-protein coupling.
Why it matters
If N-terminal disorder (not absence of the loop per se) blocks activation, then constraining this region by cyclization, stapling, or adding a mini-hairpin could convert the fragment from antagonist to agonist, a potentially cleaner route to amylin mimetics than re-adding the full disulfide.
Plausibility.62
Novelty.45
Impact.60
Basis · grounding3 computed/notes
[1]
structurepLDDT=58.6 over 30 aa indicates substantial disorder in the predicted bound state; N-terminal segment most likely disordered without the native disulfide scaffold
[2]
noteFull amylin carries a Cys2-Cys7 disulfide ring; 8-37 fragment lacks this, removing structural constraint from the N-terminal activation segment
[3]
sequenceSequence ATQRLANFLVHSSNNFGAILSSTNVGSNTY: residues 1-8 (ATQRLANF) include the hydrophobic Phe at position 8 which in full amylin participates in TMD engagement
openupdated 2026-06-11

Is the polar, asparagine-rich segment in the middle of this peptide a main part that locks onto the amylin receptors regardless of subtype?

If true, this central segment could define a minimal core for amylin-based compounds. Note: the segment is bounded by a phenylalanine on one side and a glycine on the other, not by two phenylalanines as sometimes stated.

The hypothesis
The Asn-rich mid-segment (positions 13-17: SSNNN, broadly the SSNNF region) of amylin(8-37) adopts a beta-turn or polyproline-II-like conformation when bound to the CTR extracellular domain, and this segment, not the C-terminal SNTY region, is the primary ECD-anchoring contact that persists regardless of RAMP identity.
Why it’s plausible
Sequence ATQRLANFLVHSSNNFGAILSSTNVGSNTY contains a polar cluster HSSNNFG (positions 11-17) flanked by hydrophobic Phe residues (F8 and F17), a classic beta-turn-inducing motif pattern. The ipTM=0.80 suggests stable complex formation consistent with a defined binding contact, while pLDDT=58.6 localizes disorder to peripheral rather than core-contact regions. RAMP-independent contacts would anchor the fragment across all AMY subtypes.
Why it matters
Identifying a RAMP-independent core contact region in amylin(8-37) would define a minimal pharmacophore conserved across all AMY receptor subtypes, providing a template for pan-AMY or scaffold-constrained analogs.
Plausibility.42
Novelty.55
Impact.50
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceSequence ATQRLANFLVHSSNNFGAILSSTNVGSNTY contains HSSNNFG (residues 11-17): an asparagine-rich polar segment flanked by Phe8 and Phe17, a pattern associated with beta-turn formation and ECD anchoring in class B GPCR ligands
[2]
structureipTM=0.80 indicates confident predicted interface between peptide and CTR/RAMP complex, consistent with at least one well-defined contact region
[3]
paper
RAMP1 and RAMP2 ECD binding is differentially sensitive to Y25A mutation, implying that other regions make RAMP-common contacts, pointing to the mid-segment as the likely shared anchor
doi: 10.1074/jbc.m115.713628
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.8026445508003235 boltz-2
ranking score 0.6297109127044678 boltz-2
3-letter notation
Ala-Thr-Gln-Arg-Leu-Ala-Asn-Phe-Leu-Val-His-Ser-Ser-Asn-Asn-Phe-Gly-Ala-Ile-Leu-Ser-Ser-Thr-Asn-Val-Gly-Ser-Asn-Thr-Tyr
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategycolabfold_local
runtime
predicted by
predicted at2026-05-22
citationbibtex
peptidemodel (2026). Amylin fragment (8-37): lab research tool (pep-10499, v1). PeptideModel. https://peptidemodel.com/card/pep-10499
@peptide{pep10499,
  sequence = {ATQRLANFLVHSSNNFGAILSSTNVGSNTY},
  target   = {calcr},
  author   = {peptidemodel},
  year     = {2026},
  status   = {synthesized}
}
related peptides 5 by signal overlap
clinical trials 131 on ct.gov · 1 on EUCTR · checked 2026-05-22
ct.gov trials 131
with results 58
EUCTR 1
PubMed reviews 1
by phase
1phase 11phase 23phase 31phase 44no phase
by status
7completed1recruiting1active1terminated
references 6 papers
discussion no comments
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