[Trp63, 64]-C3a (63-77)

Product Name: [Trp63, 64]-C3a (63-77)

Sequence One Letter Code: WWGKKYRASKLGLAR

Sequence Three Letter Code: H-Trp-Trp-Gly-Lys-Lys-Tyr-Arg-Ala-Ser-Lys-Leu-Gly-Leu-Ala-Arg-OH

Cas No: 130154-64-2

Chemical Formula:C86H134N26O18

Molecular Weight: 1820.3

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Inflammation and Immunology Research

SMILES: C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC4=CNC5=CC=CC=C54)N

IUPAC: (2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoic acid

INCHIKEY: WZZZEVMVZFWLNO-QYEYXIDWSA-N

INCHI:

InChI=1S/C86H134N26O18/c1-47(2)37-65(75(120)99-45-71(116)104-66(38-48(3)4)81(126)102-49(5)72(117)108-64(84(129)130)27-18-36-96-86(93)94)110-79(124)62(25-13-16-34-89)107-83(128)69(46-113)112-73(118)50(6)101-77(122)63(26-17-35-95-85(91)92)106-82(127)67(39-51-28-30-54(114)31-29-51)111-80(125)61(24-12-15-33-88)105-78(123)60(23-11-14-32-87)103-70(115)44-100-76(121)68(41-53-43-98-59-22-10-8-20-56(53)59)109-74(119)57(90)40-52-42-97-58-21-9-7-19-55(52)58/h7-10,19-22,28-31,42-43,47-50,57,60-69,97-98,113-114H,11-18,23-27,32-41,44-46,87-90H2,1-6H3,(H,99,120)(H,100,121)(H,101,122)(H,102,126)(H,103,115)(H,104,116)(H,105,123)(H,106,127)(H,107,128)(H,108,117)(H,109,119)(H,110,124)(H,111,125)(H,112,118)(H,129,130)(H4,91,92,95)(H4,93,94,96)/t49-,50-,57-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-/m0/s1

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: C3aR Agonist Peptide (C3a Analogue with Trp63/64 Substitutions) is a C-terminal analogue of complement factor C3a engineered with tryptophan substitutions at positions 63 and 64, which enhance receptor interaction. The peptide functions as an agonist of the C3a receptor (C3aR) and selectively binds to C3a receptors in vitro. Activation of C3aR by this peptide induces degranulation in C3aR-expressing cells and produces rapid, transient hypertensive responses in animal models following intravenous administration. Due to its defined receptor activity, this peptide is widely used to study C3a receptor signaling, complement-mediated inflammation, innate immune responses, and cardiovascular effects associated with complement activation.

Current Research: The complement system is a key component of innate immunity that rapidly responds to pathogens, damaged cells, and immune complexes. Activation of the complement cascade generates several biologically active fragments known as anaphylatoxins, including C3a, C4a, and C5a. These peptides function as potent inflammatory mediators that influence vascular responses, immune cell activation, and host defense. Among them, C3a exerts its biological effects through interaction with the C3a receptor (C3aR), a G protein–coupled receptor expressed on many immune and vascular cell types. The C3aR agonist peptide containing Trp63/64 substitutions is a synthetic analogue derived from the C-terminal region of C3a. The introduction of tryptophan residues enhances receptor interaction and produces a peptide that can selectively activate C3aR. Because of its defined receptor specificity and predictable biological effects, this analogue is widely used as a research tool for studying complement-mediated signaling and inflammatory responses. The Complement System and Anaphylatoxin Signaling Complement activation occurs through three primary pathways: classical, lectin, and alternative pathways. Regardless of the initiating mechanism, these pathways converge at the activation of complement component C3, which is cleaved into two fragments: C3a, an anaphylatoxin that functions as a signaling peptide C3b, which participates in opsonization and complement amplification C3a binds to the C3a receptor (C3aR) on the surface of immune cells, endothelial cells, and other tissues. Activation of this receptor triggers intracellular signaling pathways that contribute to: Recruitment and activation of immune cells Release of inflammatory mediators Changes in vascular permeability Regulation of immune responses These processes help coordinate the early stages of immune defense and inflammation. Design of the C3aR Agonist Peptide The C3aR agonist peptide is engineered from the C-terminal region of C3a, which contains the structural determinants required for receptor activation. In this analogue, tryptophan substitutions at positions 63 and 64 enhance the peptide’s interaction with the receptor. Tryptophan residues are bulky aromatic amino acids that can strengthen interactions with receptor binding pockets through hydrophobic and π-stacking interactions. Introducing these substitutions improves receptor affinity and increases the peptide’s ability to activate C3aR. As a result, the modified peptide acts as a selective agonist, capable of stimulating C3a receptors in experimental systems. Activation of C3aR Signaling When the agonist peptide binds to C3aR, it triggers signaling pathways characteristic of G protein–coupled receptor activation. These pathways often involve: Intracellular calcium mobilization Activation of protein kinase signaling cascades Release of inflammatory mediators One commonly observed cellular response is degranulation in cells expressing C3aR, such as mast cells and other immune cells. Degranulation leads to the release of bioactive molecules that contribute to inflammatory signaling and immune responses. Physiological Effects in Experimental Models In animal models, activation of C3aR by this peptide has been shown to produce rapid and transient hypertensive responses following intravenous administration. These responses reflect the influence of complement signaling on vascular tone and cardiovascular regulation. Complement-derived peptides are known to affect vascular smooth muscle activity, endothelial signaling, and inflammatory mediator release, all of which can contribute to changes in blood pressure and vascular reactivity. These physiological responses make the peptide a useful probe for studying the cardiovascular effects of complement activation. Applications in Complement and Immunology Research Because of its ability to selectively activate the C3a receptor, the peptide is widely used in experimental studies investigating complement signaling pathways. Researchers commonly employ it to explore: C3a receptor signaling mechanisms Immune cell activation and degranulation Inflammatory responses triggered by complement activation Cross-talk between complement pathways and other immune signaling systems Such studies help clarify how complement components influence immune system behavior during infection, inflammation, and tissue injury. Use in Cardiovascular and Inflammation Studies Complement activation can influence vascular function, inflammatory responses, and immune-mediated disease processes. The C3aR agonist peptide provides a convenient way to study these effects in controlled experimental settings. By selectively activating C3a receptors, researchers can analyze how complement signaling contributes to vascular responses, immune cell recruitment, and inflammatory mediator production. These investigations are relevant to understanding conditions in which complement activation plays a role, including inflammatory disorders and immune-mediated diseases. A Tool for Studying Complement Receptor Biology Synthetic analogues of complement peptides provide valuable tools for dissecting complex immune signaling pathways. The C3aR agonist peptide with Trp63/64 substitutions represents a modified form of the C3a C-terminal region that selectively activates C3a receptors. Through its ability to induce receptor-mediated cellular responses and vascular effects, this peptide supports research into complement biology, innate immune signaling, inflammation, and cardiovascular responses associated with complement activation.