Amylin (22-27) [NMeG24, NMeI26], human (IAPP)

Product Name: Amylin (22-27) [NMeG24, NMeI26], human (IAPP)

Sequence One Letter Code: NF-(NMe-G)-A-(NMe-I)-L

Sequence Three Letter Code: H-Asn-Phe-(NMe-Gly)-Ala-(NMe-Ile)-Leu-OH

Molecular Weight: 661.8

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Diabetes and Metabolic Syndrome

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: N-Methylated hIAPP(22–27) Peptide Inhibitor corresponds to residues 22–27 of human islet amyloid polypeptide (hIAPP) and contains N-methyl modifications at Gly24 and Ile26. These structural modifications disrupt backbone hydrogen bonding within the amyloidogenic core sequence NFGAIL, preventing β-sheet formation and converting the fragment into a non-amyloidogenic and non-cytotoxic peptide. Despite its reduced aggregation propensity, the peptide maintains high-affinity binding to full-length hIAPP and effectively inhibits amyloid fibril formation. This property makes it a valuable research reagent for studying amyloid inhibition mechanisms, peptide–peptide interactions, and aggregation pathways. The peptide is widely used in investigations of islet amyloid formation, β-cell toxicity, and therapeutic strategies targeting amyloid deposition in diabetes research.

Current Research: Aggregation of human islet amyloid polypeptide (hIAPP) is a hallmark feature of pancreatic islet pathology associated with type 2 diabetes. hIAPP, also known as amylin, is a hormone co-secreted with insulin by pancreatic β-cells and plays roles in glucose regulation and satiety signaling. Under pathological conditions, however, hIAPP can misfold and form amyloid fibrils, which accumulate within pancreatic islets and contribute to β-cell dysfunction and loss. To better understand the mechanisms of amyloid formation and identify strategies that prevent toxic aggregation, researchers have developed modified peptide fragments that interact with hIAPP but resist self-assembly. One such reagent is the N-methylated hIAPP(22–27) peptide inhibitor. The Amyloidogenic Core of hIAPP The sequence NFGAIL (residues 22–27) within hIAPP is widely recognized as the amyloidogenic core region responsible for initiating fibril formation. This short segment strongly promotes β-sheet assembly, which is a defining structural feature of amyloid fibrils. During aggregation, individual hIAPP molecules align and interact through backbone hydrogen bonding along this core region. These interactions promote the formation of stable β-sheet structures that stack into fibrils and eventually deposit as amyloid within pancreatic islets. Because this region is central to the aggregation process, it has become a major target for designing aggregation inhibitors that can bind to hIAPP while preventing the formation of fibrillar structures. N-Methylation Strategy to Disrupt Amyloid Formation The N-methylated hIAPP(22–27) peptide inhibitor incorporates specific chemical modifications designed to block β-sheet formation. In this peptide, N-methyl groups are introduced at Gly24 and Ile26 within the NFGAIL sequence. N-methylation alters the peptide backbone by replacing a hydrogen atom on the amide nitrogen with a methyl group. This modification has two important consequences: It disrupts backbone hydrogen bonding, which is required for β-sheet assembly. It introduces steric constraints that interfere with the alignment of peptide strands. As a result, the modified peptide cannot participate in the intermolecular hydrogen bonding networks that drive amyloid fibril formation. Conversion to a Non-Amyloidogenic Fragment Because of these structural modifications, the N-methylated peptide becomes non-amyloidogenic and non-cytotoxic. Unlike the native NFGAIL sequence, the modified fragment does not readily self-assemble into fibrillar structures. Despite its inability to form fibrils, the peptide still retains strong binding affinity for full-length hIAPP. This allows the modified fragment to interact with hIAPP molecules during the early stages of aggregation. By binding to the amyloidogenic region of hIAPP, the peptide interferes with the molecular interactions required for fibril growth, effectively acting as a competitive inhibitor of amyloid formation. Mechanism of Amyloid Inhibition The inhibitory activity of the N-methylated hIAPP fragment is based on its ability to bind aggregation-prone hIAPP intermediates while preventing β-sheet propagation. This interaction disrupts the nucleation and elongation steps of fibril formation. In experimental systems, the peptide can inhibit amyloid formation by: Blocking intermolecular β-sheet interactions Stabilizing non-aggregating peptide complexes Preventing the growth of fibrillar structures Through these mechanisms, the modified fragment helps researchers study how amyloid aggregation can be disrupted at the molecular level. Applications in Amyloid and Diabetes Research The N-methylated hIAPP(22–27) peptide is widely used as a research tool for investigating amyloid inhibition mechanisms. Because it selectively interacts with the amyloidogenic region of hIAPP, it allows scientists to analyze how structural modifications influence aggregation pathways. Common research applications include: Studying peptide–peptide interactions during amyloid formation Investigating early aggregation intermediates of hIAPP Evaluating mechanisms of amyloid inhibition Examining structure–activity relationships in amyloidogenic sequences These experiments help clarify the molecular events that lead to hIAPP aggregation and islet amyloid formation. Relevance to β-Cell Toxicity Amyloid deposition within pancreatic islets is strongly associated with β-cell dysfunction and loss in type 2 diabetes. Aggregating hIAPP species can damage cellular membranes, disrupt mitochondrial function, and trigger stress responses that lead to cell death. By inhibiting fibril formation and stabilizing non-toxic peptide interactions, modified fragments such as the N-methylated hIAPP inhibitor provide useful models for studying mechanisms that protect β-cells from amyloid toxicity. Supporting Therapeutic Research Understanding how amyloid formation can be prevented is an important goal in metabolic disease research. Peptides that disrupt aggregation provide insight into how structure-based inhibitors might be designed to block amyloid deposition in pancreatic tissue. The N-methylated hIAPP(22–27) peptide inhibitor serves as a valuable experimental probe for exploring these strategies. By maintaining strong binding to hIAPP while preventing β-sheet formation, it helps researchers investigate aggregation pathways, amyloid inhibition mechanisms, and potential therapeutic approaches targeting islet amyloid formation in diabetes.